Renal replacement therapy device for controlling fluid balance of treated patient

ABSTRACT

A first flow path is defined within a first panel that forms a part of an extracorporeal fluid circuit. A second flow path is defined within a second panel that also forms a part of the extracorporeal fluid circuit. The first and second panels are oriented in a fluid processing cartridge for mounting as an integrated unit on a fluid processing machine and for removal as an integrated unit from the fluid processing machine.

RELATED APPLICATIONS

[0001] This application is a continuation-in-part of co-pending U.S.patent application Ser. No. 08/800,881, filed Feb. 14, 1997, andentitled “Hemofiltration System,” which is incorporated herein byreference. This application is also a divisional of co-pending U.S.patent application Ser. No. 09/451,238, filed Nov. 29, 1999, andentitled “Systems and Methods for Performing Frequent Hemofiltration,”which is incorporated herein by reference.

FIELD OF THE INVENTION

[0002] This invention relates to systems and methods for processingblood, e.g., for filtration, pheresis, or other diagnostic ortherapeutic purposes.

BACKGROUND OF THE INVENTION

[0003] There are many types of continuous and intermittent bloodprocessing systems, each providing different therapeutic effects anddemanding different processing criteria.

[0004] For example, hemofiltration emulates normal kidney activities foran individual whose renal function is impaired or lacking. Duringhemofiltration, blood from the individual is conveyed in anextracorporeal path along a semipermeable membrane, across which apressure difference (called transmembrane pressure) exists. The pores ofthe membrane have a molecular weight cut-off that can thereby passliquid and uremic toxins carried in blood. However, the membrane porescan not pass formed cellular blood elements and plasma proteins. Thesecomponents are retained and returned to the individual with thetoxin-depleted blood. Membranes indicated for hemofiltration arecommercially available and can be acquired from, e.g., Asahi Medical Co.(Oita, Japan).

[0005] After hemofiltration, fresh physiologic fluid is supplied totoxin-depleted blood. This fluid, called replacement fluid, is bufferedeither with bicarbonate, lactate, or acetate. The replacement fluidrestores, at least partially, a normal physiologic fluid andelectrolytic balance to the blood. Usually, an ultrafiltration functionis also performed during hemofiltration, by which liquid is replaced inan amount slightly less than that removed. Ultrafiltration decreases theoverall fluid level of the individual, which typically increases, in theabsence of ultrafiltration, due to normal fluid intake between treatmentsessions.

[0006] Following hemofiltration, fluid balancing, and ultrafiltration,the blood is returned to the individual.

SUMMARY OF THE INVENTION

[0007] One aspect of the invention provides a fluid processing systemcomprising an extracorporeal circuit for circulating a fluid from anindividual through a filter to remove waste and to return fluid to theindividual after removal of waste. A first portion of the extracorporealcircuit is integrated, at least in part, within a first panel. A secondportion of the extracorporeal circuit is integrated, at least in part,within a second panel. The system further includes a fluid processingcartridge, which orients the first and second panels for mounting as anintegrated unit on a fluid processing machine and for removal as anintegrated unit from the fluid processing machine.

[0008] In one embodiment, the first portion of the extracoporeal circuithandles waste fluid, and the second portion of the extracoporeal circuithandles replacement fluid for return to the individual.

[0009] In one embodiment, the first and second portions of theextracorporeal circuit include in-line chambers that volumetricallybalance waste fluid removed from the individual and waste replacementfluid returned to the individual. The in-line chambers can occupy afixed volume cavity on the fluid processing machine, whereby the in-linechambers possess a volume defined by the fixed volume cavity on themachine.

[0010] In one embodiment, at least one of the first and second panelsincludes an operative region that flexes in response to an externalforce applied by the fluid processing machine. The operative region cancomprise, e.g., an in-line clamping region that flexes to occlude fluidflow, or an in-line pump tube that flexes in response to peristalticforce to pump fluid, or an operative region that permits sensing of aflow condition by a sensor on the fluid processing machine.

[0011] In one embodiment, the fluid processing cartridge includes a traycontaining the first and second panels, which are oriented within thetray in an overlaying relationship.

[0012] Another aspect of the invention provides a blood processingsystem. The system comprises an extracoporeal fluid circuit. The circuitincludes a first flexible panel having a pattern of seals defining afirst flow path that forms a part of the extracorporeal fluid circuit.The circuit also includes a second flexible panel having a pattern ofseals defining a second flow path that forms another part of theextracorporeal fluid circuit. A fluid processing cartridge retains thefirst and second flexible panels in an overlaying relationship. Thesystem further includes a fluid processing device including a chassis toremovably mount the fluid processing cartridge with the first flexiblepanel oriented adjacent to the chassis. The fluid processing deviceincludes an actuator on the chassis operating to apply force through thefirst flexible panel to a region of the second flexible panel to eitherpump fluid in the second flow path or occlude flow in the second flowpath.

[0013] The actuator can comprise, e.g. a pump element to apply aperistaltic force to the region of the second flexible panel through thefirst flexible panel, or an in-line pump tube to which the peristalticforce is applied, or a clamp element to apply an occlusion force to theregion of the second flexible panel through the first flexible panel.

[0014] In one embodiment, a sensor on the chassis senses a flowcondition in the second flow path through the first and second flexiblepanels.

[0015] In one embodiment, the fluid processing cartridge includes a traymovable into and out of association with the chassis. In onearrangement, the tray includes a cut-out exposing a region of the firstflexible panel to the actuator.

[0016] Another aspect of the invention provides a hemofiltrationmachine. The machine includes a chassis and an operating element on thechassis comprising at least one of a peristaltic pump, a clamp, and asensor. A door is movable with respect to the chassis between a firstposition enabling mounting of a fluid processing cartridge on thechassis and a second position holding the fluid processing cartridge onthe chassis in a predetermined orientation with the operating element.

[0017] In one embodiment, the door moves in a path toward and away fromthe chassis.

[0018] In one embodiment, a depression on the chassis defines a space ofknown volume to accommodate a fluid balancing chamber carried in thefluid processing cartridge.

[0019] In one embodiment, the door includes at least one pump race forregistry with a pump region carried in the fluid processing cartridge.

[0020] Another aspect of the invention provides a fluid processingmethod. The method establishes an extracoporeal fluid circuit thatcommunicates with a filter. The method defines within a first panel afirst flow path that forms a part of the extracorporeal fluid circuit,while defining within a second panel a second flow path that formsanother part of the extracorporeal fluid circuit. The method orients thefirst and second panels in a fluid processing cartridge for mounting asan integrated unit on a fluid processing machine and for removal as anintegrated unit from the fluid processing machine.

[0021] In one embodiment, the method orients the first and second panelsin an overlaying relationship.

[0022] Other features and advantages of the inventions are set forth inthe following specification and attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0023]FIG. 1 is a diagrammatic view of a system that enables frequenthemofiltration by supplying to a treatment location a durablehemofiltration machine, a disposable fluid processing cartridge thatfits on the machine, ancillary processing materials that the machine andcartridge use, and telemetry that supports the hemofiltration therapy;

[0024]FIG. 2 is a front perspective view of a hemofiltration machinethat the system shown in FIG. 1 supplies to a treatment location;

[0025] FIGS. 3 to 5 are side elevation views showing the loading intothe machine shown in FIG. 2 of a fluid processing cartridge, which thesystem shown in FIG. 1 also supplies to the treatment location;

[0026]FIG. 6A is a perspective view of the inside of the door of thehemofiltration machine shown in FIG. 2;

[0027]FIG. 6B is a side section view of a spring loaded pump racecarried on the door shown in FIG. 6A, taken generally along line 6B-6Bin FIG. 6A;

[0028]FIG. 7 is an exploded perspective view of one embodiment of thefluid processing cartridge that is supplied to the treatment location,comprising a tray in which a fluid processing circuit is contained;

[0029]FIG. 8 is an assembled perspective view of the fluid processingcartridge shown in FIG. 7;

[0030]FIG. 9 is a side section view of the fluid processing cartridgeshown in FIGS. 7 and 8, showing the cartridge as it is supplied in aclosed, sterile condition to the treatment location;

[0031]FIG. 10 is a perspective view of the cartridge shown in FIGS. 7 to9, in preparation of being mounted on the hemofiltration machine shownin FIG. 2;

[0032]FIG. 11 is an embodiment of a fluid circuit that the cartridgeshown in FIG. 10 can incorporate, being shown in association with thepumps, valves, and sensors of the hemofiltration machine shown in FIG.2;

[0033]FIGS. 12A and 12B are largely schematic side section views of oneembodiment of fluid balancing compartments that can form a part of thecircuit shown in FIG. 11, showing their function of volumetricallybalancing replacement fluid with waste fluid;

[0034]FIGS. 13A, 13B, and 13C are perspective views of a bag configuredwith a pattern of seals and folded over to define a overlaying flexiblefluid circuit that can be placed in a fluid processing cartridge of atype shown in FIG. 11;

[0035]FIG. 14 is a plane view of the pattern of seals that the bag shownin FIGS. 13A, 13B, and 13C carries, before the bag is folded over onitself;

[0036]FIG. 15 is a plane view of the overlaying fluid circuit that thebag shown in FIG. 14 forms after having been folded over on itself;

[0037]FIG. 16 is a largely schematic side section view of the overlayingfluid balancing compartments that are part of the circuit shown in FIG.15, showing their function of volumetrically balancing replacement fluidwith waste fluid;

[0038]FIG. 17 is a front perspective view of an embodiment of a chassispanel that the hemofiltration machine shown in FIG. 2 can incorporate;

[0039]FIG. 18 is a back perspective view of the chassis panel shown inFIG. 17, showing the mechanical linkage of motors, pumps, and valveelements carried by the chassis panel;

[0040]FIG. 19 is a diagrammatic view of a telemetry network that canform a part of the system shown in FIG. 1;

[0041]FIG. 20 is a diagrammatic view of overlays for imparting controllogic to the machine shown in FIG. 2;

[0042]FIG. 21 is an embodiment of a set for attaching multiplereplacement fluid bags to the cartridge shown in FIG. 10, the setincluding an in-line sterilizing filter;

[0043]FIG. 22 is a plane view of a graphical user interface that thehemofiltration machine shown in FIG. 2 can incorporate; and

[0044]FIG. 23 is a perspective view of a generic user interface whichcan be customized by use of a family of interface templates, which thehemofiltration machine shown in FIG. 2 can incorporate.

[0045] The invention may be embodied in several forms without departingfrom its spirit or essential characteristics. The scope of the inventionis defined in the appended claims, rather than in the specificdescription preceding them. All embodiments that fall within the meaningand range of equivalency of the claims are therefore intended to beembraced by the claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0046] The various aspects of the invention will be described inconnection with providing hemofiltration. That is because the featuresand advantages that arise due to the invention are well suited to theperformance of hemofiltration. Still, it should be appreciated that thevarious aspects of the invention can be applied to achieve other bloodprocessing objectives as well, such as hemodialysis and hemopheresis.

[0047] I. System for Providing Frequent Hemofiltration

[0048]FIG. 1 shows a system 10 that makes it possible for a person whoserenal function is impaired or lacking, to receive convenient andtherapeutically effective hemofiltration on a frequent basis, e.g., atleast four times weekly and, preferably, six times weekly. The frequenthemofiltration therapy that the system 10 provides has as one of itsobjectives the maintenance of uremic toxin levels in the person's bloodwithin a comfortable range, e.g., at no more than 80% of the maximumlevel. Through frequent hemofiltration, the system 10 can provide eitheracute or chronic treatment of renal impairment or failure.

[0049] The system 10 delivers the durable and disposable equipment andmaterials necessary to perform frequent hemofiltration on the person ata designated treatment location 12.

[0050] The location 12 can vary. It can, for example, be a setting wheresupport and assistance by one or more medically trained care givers areimmediately available to the person, such as at a hospital, anoutpatient clinic, or another treatment center. Alternatively, thelocation 12 can comprise a setting where support or assistance areprovided by a trained partner, such as in the person's residence.

[0051] By careful design of durable and disposable equipment, the system10 can make it possible for the person to perform frequencyhemofiltration in a non-clinical setting, without direct assistance fromtechnically or medically trained persons.

[0052] To make frequent hemofiltration more convenient, the personpreferably has been fitted with one or more vascular access devices 14.Each device 14, for example, may be generally constructed in the mannerdisclosed in pending U.S. patent application Ser. No. 08/724,948, filedNov. 20, 1996, and entitled “Subcutaneously Implanted Cannula and Methodfor Arterial Access.”

[0053] The devices 14 preferably support high blood flow rates at orabove 300 ml/min and preferably at least 600 ml/min. The devices 14 alsoenable quick and frequent cannulation. The devices 14 thereby reduce thetime required to set up, perform, and complete a frequent hemofiltrationsession. The high blood flow rates that the devices 14 support alsoincrease the removal rate of uremic toxins during hemofiltration, aswill be described in greater detail later.

[0054] To enable frequent hemofiltration, the system 10 supplies to thetreatment location 12 a durable hemofiltration machine 16. The system 10also supplies fluid processing cartridges 18 to the treatment location12, for installation on the machine 16 at the time of treatment. Thesystem 10 further supplies ancillary materials 20, such as replacementfluids, to the treatment location 12 for use in association with thecartridge 18 and machine 16. The system 10 also preferably supplies atelemetry network 22, to enable centralized, off-site monitoring andsupervision of the frequent hemofiltration treatment regime.

[0055] The operation of the system 10 to provide these various functionswill now be described in greater detail.

[0056] A. Supplying a Hemofiltration Machine

[0057] The system 10 includes a source 24 that supplies a hemofiltrationmachine 16 (which can also be called a “cycler”) to the treatmentlocation 12. The machine 16 is intended to be a durable item capable oflong term, maintenance free use.

[0058]FIG. 2 shows a representative embodiment of a machine 16 capableof performing frequent hemofiltration. The machine 16 is preferablylightweight and portable, presenting a compact footprint, suited foroperation on a table Lop or other relatively small surface normallyfound, e.g., in a hospital room or in a home. The compact size of themachine 16 also makes it well suited for shipment to a remote servicedepot for maintenance and repair.

[0059] In the illustrated embodiment, the machine 16 includes a chassispanel 26 and a panel door 28 that moves on a pair of rails 31 in a pathtoward and away from the chassis panel 26 (as shown by arrows in FIG.2). A slot 27 is formed between the chassis panel 26 and the door 28. AsFIGS. 3 to 4 show, when the door 28 is positioned away from the panel26, the operator can, in a simple vertical motion, move a fluidprocessing cartridge 18 into the slot 27 and, in a simple horizontalmotion, fit the cartridge 1B onto a raised portion of the chassis panel26. When properly oriented, the fluid processing cartridge 18 rest onthe rails 31 to help position the cartridge 18. As FIG. 5 shows,movement of the door 28 toward the panel 26 engages and further supportsthe cartridge 18 for use on the panel 26 for use. This position of thedoor 28 will be called the closed position.

[0060] The machine 16 preferably includes a latching mechanism 30 and asensor 32 (see FIG. 2) to secure the door 28 and cartridge againstmovement before enabling circulation of fluid through the cartridge 18.

[0061] As will be described in greater detail later, the processingcartridge 18 provides the blood and fluid interface for the machine 16.

[0062] The machine 16 pumps blood from the person, through the fluidprocessing cartridge 18 to a hemofilter 34 (mounted in brackets to theside of the chassis panel 26, as shown in phantom lines in FIGS. 2 to5), back to the cartridge 18, and then back to the person.

[0063] Alternatively, the hemofilter 34 can form an integrated part ofthe cartridge 18. The hemofilter 34 is connected via the cartridge 1B tothe person's blood supply through the vascular access devices 14.

[0064] The machine 16 includes a blood handling unit 36 mounted on thechassis panel 26. The blood handling unit 36 includes a peristalticblood pump 92 and various clamping and sensing devices (describedlater). The blood handling unit 36 circulates the person's blood in acontrolled fashion through the hemofilter 34 and back to the person. Thehemofilter 34 removes waste fluid containing urea and other toxins.

[0065] The machine 16 also includes a fluid management unit 38 mountedon the chassis panel 26. The fluid management unit 38 includes aperistaltic waste and replacement fluid pump 152 and various clampingand sensing devices (described later). The fluid management unit 38replaces the waste fluid with a sterile replacement fluid, for returnwith the treated blood to the person's blood supply. The replacementfluid also acts to maintain the person's electrolytic balance andacid/base balance.

[0066] The fluid management unit 38 includes a fluid balancing element40 mounted on the chassis panel 26. The fluid balancing element 40meters the return replacement fluid in proportion to the amount of wastefluid removed.

[0067] In the illustrated embodiment, the fluid balancing element 40includes one or more balancing chambers 206, 208 and associated clampingdevices (the details of which will be described later). The chambers206, 208 comprise preformed depressions formed in the raised portion ofthe chassis panel 26. As FIG. 6A shows, preformed depressions on thedoor 28 form mating chambers 206′, 208′, which register with the chassispanel chambers 206, 208. When the door 28 is closed, the registeredchambers 206/206′ and 208/208′ define between them spaces of knownvolume, e.g., 20 ml. The known volume can, of course, be greater or lessthan 20 ml, and the chambers 206/206′ and 208/208′ can each have adifferent known volume.

[0068] As will be described in greater detail later, flexible containers212 and 214, which form a part of a preformed fluid circuit carriedwithin the fluid processing cartridge 18, fit into the registeredchambers 206/206′ and 208/208′. The chambers 206/206′ and 208/208′ andassociated clamping devices interact with the containers 212 and 214, toprovide the capability of balancing waste and replacement fluidvolumetrically, in an accurate, straightforward manner, without use ofweigh scales and weight sensing.

[0069] The machine 16 also includes an ultrafiltration unit 42 on thechassis panel 26. The ultrafiltration unit 42 includes a peristalticultrafiltration pump 144 to remove additional waste from the personwithout addition of replacement fluid. The machine 16 provides, at theend of each frequent hemofiltration session, a net ultrafiltration fluidloss, which coincides with an amount prescribed by the attendingphysician.

[0070] The machine 16 completes a frequent hemofiltration session when aprescribed replacement fluid volume has been exchanged and the netultrafiltration fluid loss target has been met. The machine 16 canaccommodate continuous or extended treatment sessions on an automatedbasis. The machine 16 can also accommodate operation based uponindividually set ultrafiltration rates, blood flow rates, or returnfluid flow rates, with completion determined by the volume ofreplacement fluid exchanged or by a treatment timer.

[0071] As will be described in greater detail later, the variouspumping, clamping, and sensing devices on the machine 16 provide bloodflow, fluid management, and safety functions by sensing pump pressures,detecting air, detecting blood leak through the hemofilter 34, andsensing waste pressure. The sensors also provide addition fluidmanagement and safety functions, such as sensing replacement fluidtemperature and replacement fluid pump pressure. The machine 16 alsoprovides other processing functions, such as priming, supplying areplacement fluid bolus, and carrying out a rinseback of the person'sblood.

[0072] The machine 16 also preferable includes an operator interface 44,which, in the illustrated embodiment (see FIG. 2) is carried on theexterior of the door 2B. As will be described later, the interface 44provides simple switch and/or knob operation of the machine 16,preferably by use of one hand. The interface 44 displays informationnecessary to operate the machine 16, presenting an uncluttered displayand tactile touch buttons to intuitively lead a person without technicalor medical background through set up and operation of the machine 16with a minimum of training.

[0073] Further details of the machine 16, the pumps and sensing devices,and their interaction with the fluid processing cartridge 18 will bedescribed later.

[0074] The source 24 supplying the machine 16 can comprise a company orbusiness that manufactures the machine 16 or otherwise distributes themachine 16 to the treatment location 12 on a sale, lease, or rentalbasis.

[0075] B. Supplying a Fluid Processing Cartridge

[0076] The system 10 further includes a source 46 for supplying a fluidprocessing cartridge 18 to the treatment location 12 for use inassociation with the machine 16. The cartridge 18 is intended to bedisposable item, capable of single or extended use, which the loads onthe machine 16 before beginning a hemofiltration session (as FIGS. 3 to5 show). The cartridge 18 can be removed from the machine 16 anddiscarded upon the completing the hemofiltration session, or its use canbe extended to one or more subsequent sessions , as will be describedlater.

[0077] The cartridge 18 couples to the person's vascular access devices14 and interacts with the machine 16 to draw, process, and return bloodin a continuous, extracoporeal path, to carry out fluid balancingthrough waste removal, replacement fluid exchange, and ultrafiltration.

[0078] Preferably, the tasks of loading and unloading the cartridge 18are simple and straightforward, following a simple, straight loading andunloading path into the slot 27 and against the chassis panel 26, asFIGS. 3 to 5 show. In this way, the person receiving hemofiltration canby himself/herself set up the cartridge 18 and machine 16, withoutnecessarily requiring assistance from a technically or medically trainedperson.

[0079] The cartridge 18 preferably provides the entire blood and fluidinterface for the machine 16, including all pumping, valving, pressuresensing, air detection, blood leak detection, and tubing management. Thecartridge 18 preferable is supplied to the treatment location 12 withall tubing, access needles and waste and replacement fluid connectionspreconnected. A waste bag also can be preattached, if desired, or thewaste line can be placed in a drain.

[0080] Loading the cartridge 18 on the chassis panel 26 and closing thedoor 28 also automatically locates all sensors of the machine's safetyfunction in association with the blood fluid interface. The operator isnot required to load anything else to carry out the machine's safetyfunction. Once the machine 18 undergoes start up testing to confirmcartridge placement and integrity and to confirm the functionality ofthe sensors, subsequent automated operation the machine 18 in a safemode is assured.

[0081] The cartridge 18 can be constructed in various ways. In theillustrated embodiment (see FIGS. 7 to 9), the cartridge 18 includes apreformed tray 48 and insert 53 manufactured, e.g., by thermoformingpolystyrene or another comparable material. The tray 48 and insert 53are peripherally joined together, e.g., by ultrasonic welding.

[0082] The tray includes a base 50, side walls 52, and an open top edge54. The geometry of the tray 48 is appropriately keyed to fit in onlyone orientation on the rails 31 in the slot 27 between the chassis panel26 and door 28 of the machine 16. When so fitted, the insert 53 rests onthe raised portion of the chassis panel 26. Closing the door 28 securesthe tray 48 to the panel 26.

[0083] A preformed circuit 56 is carried between the base 50 of the tray48 and the insert 53. The circuit 56 is arranged to carry blood, waste,and replacement fluid during hemofiltration.

[0084] As will be described in greater detail later, the circuit 56includes an array of fluid flow paths formed with in-line flexiblecontainers 212 and 214 (for fluid balancing), peristaltic pump headers,sensor stations, tubing, and valve stations. The layout of flow paths,containers, pump headers, sensing stations, and valve stations on thecircuit 56 form a mirror image of the layout of the structural andmechanical components on the chassis panel 26 and door 28 of the machine16.

[0085] The insert 53 includes cut outs 58 to expose the containers,peristaltic pump headers, sensing stations, and valve stations forengagement with equipment on the chassis panel 26. When the tray 48 isfitted to the chassis panel 26, and the door 28 is closed, the in-linecontainers 212/214 formed in the circuit 56 fit within the registeredchambers 206/206′ and 208/208′ on the chassis panel 26 and door 28.Likewise, the pump headers and the sensor and valve stations on thecircuit 56 overlay and engage corresponding peristaltic pumps, sensors,and valve on the chassis panel 26.

[0086] In the illustrated embodiment (see FIG. 7), the base 50 of thetray 48 underlaying the pump stations is relieved, to form pump races360. The inside surface of the door 28 carries concave pump races 362supported by springs 364 (see FIGS. 6A and 6B). When the door 28 isclosed, the spring loaded pump races 362 on the door 28 nest with therelieved pump races 360 on the tray 48, to provide rigidity and support.Alternatively, the pump races 360 can form cutouts in the base 50 (likecut outs 58 in the insert, as earlier described), through which the pumpraces 362 on the door 28 extend.

[0087] The base 50 of the tray 48 underlying the containers 212/214 isalso relieved, to form chamber supports 368. When the the door 28 isclosed, the tray supports 368 fit within the door chambers 206′ and208′. The door 28 therefore engages the tray 48, to add overall rigidityand support to the tray base 50.

[0088] When the door 28 is closed, the containers 212/214 are enclosedwithin the registered chambers 206/206′ and 208/208′ and tray chambersupports 368, which define for the containers 212/214 to a known maximumvolume. The peristaltic pumps, sensors, and valve stations on themachine 16 interact with the flexible components of the circuit 56.

[0089] The cartridge 18 makes possible direct, centralized connection ofa blood-fluid interface to the blood pump, the waste and replacementpump, the ultrafiltration pump, the fluid balancing chambers, the sensordevices, and the clamping devices of the machine 16, with no airinterfaces. The compact arrangement of the cartridge 18 also reducesfluid pressure drops, thereby accommodating high flow rates, e.g., anarterial blood line pressure drop of less than 250 mmHg at a flow rateof 600 ml/min and a hematocrit of 25.

[0090] As FIGS. 9 and 10 show, lengths of flexible tubing FT are coupledto the circuit 56 in the base 50 of the tray 48 and rest in coils on topof the insert 53 within the tray 48 during shipment and before use (seeFIG. 9). As FIG. 9 also shows, a removable lid 60, made, e.g., fromethylene oxide permeable TYVEKJ material or polyethylene plastic sheetstock, covers and seals the interior of the tray 48 prior to use. Thecartridge 1B can therefore be sterilized by exposure to ethylene oxideprior to use. Other methods of sterilization, e.g., gamma radiation orsteam sterilization, can be used. Alternatively, the ultrasonicallywelded assembly of the tray 58, insert 53, and the circuit 56 (withattached tubing FT) can be packaged as a unit into a sealed plastic bagfor sterilization, obviating the need for the lid 60.

[0091] At the instant of use, the lid 60 is peeled away, or, in thealternative arrangement, the sealed plastic bag is opened. The attachedflexible tubing FT is extended beyond the bounds of the tray 48 to makeconnection with external processing items (see FIG. 10). The tubing FTcarries appropriate couplers for this purpose. The tray 48 is movedalong a vertical path for loading into the slot 27 and then a horizontalpath for loading on the raised portion of the chassis panel 26, afterwhich a simple motion of the door latching mechanism 30 aligns theentire fluid circuit 56 with the pumps, sensors, and clamps on thechassis panel 26. There is no area of blood or fluid contact that thisoutside the disposable circuit 56.

[0092] The source 46 supplying the cartridge 18 can comprise a companyor business that manufactures the cartridge 18 or that otherwisedistributes the cartridge 18 to the treatment location 12 on a sale,lease, or rental basis.

[0093] 1. Fluid Circuit for Frequent Hemofiltration

[0094]FIG. 11 shows a representative fluid circuit 56 that is wellsuited for carrying out frequent hemofiltration, and which can beincorporated into the cartridge 18 for interface with pumps, valves, andsensors arranged as a mirror image on the chassis panel 26.

[0095] The fluid circuit 56 couples the hemofilter 34 to several mainfluid flow paths. The main fluid flow paths comprise an arterial bloodsupply path 62, a venous blood return path 64, a blood waste path 66, areplacement fluid path 68, and an ultrafiltration/fluid balancing path70.

[0096] (i) Blood Supply and Return Paths

[0097] The arterial blood supply path 62 and venous blood return path 64includes lengths of flexible tubing 72 and 74 that extend outside thetray 48 (see FIG. 10). As FIG. 10 shows, The paths 72 and 74 carrycannulas 76 at their distal ends (or connectors that enable connectionto cannulas 76), to enable connection, respectively, to the person'sarterial and venous access devices 14.

[0098] The arterial blood supply path 62 also includes a length offlexible tubing 78 (see FIG. 10) that extends outside the tray 48. Thetubing 78 includes a distal connector 80 to couple to the blood inlet 82of the hemofilter 34.

[0099] Likewise, the venous blood return path 64 includes a length offlexible tubing 84 that extends outside the tray 48. The tubing 84includes a distal connector 86 to couple to the blood outlet 88 of thehemofilter 34.

[0100] Alternatively, the hemofilter 34 can be an integral part of thetray 48. In this arrangement, the arterial and venous blood paths 78 and84 are supplied pre-connected to the hemofilter 34.

[0101] The exterior tubing components of the arterial or venous bloodpath can include injection sites 90. The sites can be used, e.g., toremove trapped air or to inject anticoagulant, medication, or buffersinto the blood flows. The exterior tubing components of the arterial orvenous blood paths can also include conventional pinch clamps, tofacilitate patient connection and disconnection.

[0102] The remaining portions of arterial and venous blood paths 62 and64 are contained in the circuit 56 held within the tray 48. The bloodpump 92 of the machine 16 engages a pump header region 94 in thearterial blood supply path 62 within the tray 48 upstream of thehemofilter 34, to convey blood into and through the hemofilter 34. Anarterial blood clamp 96 and a patient connection-disconnection (airbubble detector) sensor 98 on the machine 16 engage a clamp region 100and a sensor region 102 in the arterial blood supply path 62 within thetray 48 upstream of the blood pump 92. Alternatively, an air bubblesensor (not shown) can be located downstream of the blood pump 92 andupstream of the hemofilter 34.

[0103] The placement of the air sensor 98 upstream of the hemofilter 34allows air bubbles to be detected prior to entering the hemofilter 34.In the hemofilter 34, air bubbles break up into tiny micro-bubbles,which are not as easily detected. Placement of the air sensor 98upstream of the hemofilter 34 also serves the additional purpose ofdetecting air when the blood pump 92 is operated in reverse, to rinseback blood to the patient, as will be described later.

[0104] An air detector 108 on the machine 16 engages a sensing region110 in the venous blood return path 64 within the tray 48 downstream ofthe hemofilter 34. A venous clamp 112 on the machine 16 engages a clampregion 114 in the venous blood return path 64 within the tray 48downstream of the air detector 108.

[0105] (ii) Blood Waste Path

[0106] The membrane (not shown) located in the hemofilter 34 separateswaste including liquid and uremic toxins from the blood. A waste outlet116 conveys waste from the hemofilter 34.

[0107] The blood waste path 66 includes a length of flexible tubing 118(see FIG. 10) that extends beyond the tray 48. The tubing 118 carries adistal connector 120 to couple to the waste outlet 116 of the hemofilter34. Alternatively, when the hemofilter 34 is integrated in the tray 48,the waste path 66 can be supplied pre-connected to the hemofilter 34.

[0108] The waste path 66 also includes a length of flexible tubing 122that extends beyond the tray 48. The tubing 122 carries a connector 124to couple to a waste bag 126 or an external drain. Alternatively, thewaste bag 126 can be preconnected to the tubing 122.

[0109] The remainder of the waste path 66 is contained within thecircuit 56 inside the tray 48. A blood leak detector 128 on the machine16 engages a sensor region 130 in the waste path 66 downstream of thehemofilter 34. A waste pressure sensor 132 on the machine 16 engagesanother sensor region 134 in the waste path 66 downstream of the bloodleak detector 128.

[0110] Within the tray 48, the waste path 66 branches into anultrafiltration path 136 and a balancing path 138. The ultrafiltrationbranch path 136 bypasses in-line containers 212 and 214 of the circuit56. The ultrafiltration pump 144 on the machine 16 engages a pump headerregion 146 in the ultrafiltration branch path 136 within the tray 48.The waste balancing branch path 138 communicates with the in-linecontainers 212 and 214. The waste and replacement fluid pump 152 on themachine 16 engages a pump header region 154 in the waste balancingbranch path 3.38 within the tray 48 upstream of the in-line containers212 and 214. A pressure sensor 156 on the machine 16 engages a sensorregion 160 in the waste balancing branch path 138 within the tray 48between the waste and replacement fluid pump 152 and the in-linecontainers 212 and 214. The pressure sensor 156 senses the fluidpressure required to convey replacement fluid into the venous returnline. This resistance to the flow of replacement fluid is the venousblood pressure. The pressure sensor 156 in the waste fluid path 138thereby serves to sense the venous blood pressure.

[0111] A flush clamp 162 engages a clamp region 164 in the waste path 66within the tray 48 downstream of the in-line containers 212 and 214. Awaste clamp 166 engages a clamp region 168 in the waste path 66downstream of the flush clamp 162. The circuit 56 in the tray 48 alsocan include an air break 170, which communicates with the waste path 66downstream of the waste clamp 166. The air break 170 prevents back flowof contaminants into the circuit 56 from the waste bag 126 or drain.

[0112] (iii) Replacement Fluid Path

[0113] The replacement fluid path 68 includes a length of flexibletubing 172 that extends outside the tray 48. The tubing 172 includes adistal connector 174 or connectors that enable connection to multiplecontainers of replacement fluid 176. As will be described later, thetubing 172 can also include an in-line 0.2 m sterilizing filter 178 toavoid contamination of the circuit 56.

[0114] The containers 176 together typically hold from 8 to 20 combinedliters of replacement fluid, depending upon the fluid removal objectivesof the particular frequent hemofiltration procedure. The replacementfluid is also used to prime the fluid circuit 56 at the outset of atreatment session and to rinse back blood to the patient at the end of atreatment session.

[0115] The remainder of the replacement fluid path 68 is contained inthe circuit 56 within the tray 48. Sensing region 186 in the replacementfluid path 68 inside the tray 48 engages a replacement fluid flow ratedetector 182 on the machine 16. A clamping region 190 in the replacementfluid path 68 inside the tray 48 engages a replacement fluid clamp 188on the machine 16.

[0116] Within the tray 48, the replacement fluid path 68 includes apriming or bolus branch path 192 that communicates with the arterialblood supply path 62. A clamping region 196 in the priming branch path192 engages a priming clamp 194 on the machine 16.

[0117] Within the tray 48, the replacement fluid path 68 also includes abalancing branch path 198 that communicates with the venous blood returnpath 64, via the in-line containers 212 and 214. A pump header region200 in the balancing replacement branch path 198 engages the waste andfluid replacement pump 152 on the machine 16 upstream of the in-linecontainers 212 and 214.

[0118] In the illustrated embodiment, the waste and fluid replacementpump 152 comprises a dual header pump, simultaneously engaging the twopump header regions 154 and 200 on the waste path 66 and the replacementfluid path 68. A sensor region 204 in the balancing replacement branchpath 198 engages a pressure sensor 202 on the machine 16 between thewaste and replacement fluid pump 152 and the in-line containers 212 and214. The pressure sensor 202 senses the pressure required to conveywaste fluid into the waste return line. This resistance to the flow ofwaste fluid is the waste line pressure. The pressure sensor 202 in thereplacement fluid path 198 thereby serves to sense the waste linepressure. Similarly, as already described, the pressure sensor 156 inthe waste fluid path 138 serves to sense the venous blood pressure.

[0119] (iv) Ultrafiltration/Fluid Balancing Path

[0120] The ultrafiltration waste branch path 136 within the tray 48,which bypasses the in-line containers 212 and 214 of the circuit 56,accommodates transfer of a prescribed volume of waste to the waste bag126, without an offsetting volume of replacement fluid. The circuit 56thereby is capable of performing an ultrafiltration function.

[0121] The balancing waste branch path 138 and the balancing replacementbranch path 198 pass through the in-line containers 212 and 214 in thecircuit 56 contained within the tray 48. The in-line containers 212 and214 transfer a volume of replacement fluid to the venous blood returnpath 64 in proportion to the volume of waste fluid removed, except forthe volume making up the ultrafiltration volume loss. The circuit 56 isthereby capable of performing a fluid balancing function in addition tothe ultrafiltration function.

[0122] In the illustrated embodiment, the machine 16 and circuit 56carry out the fluid balancing function volumetrically, without weightsensing. More particularly, the registered chambers 206/206′ and208/208′ on the chassis panel 26 and door 28 of the machine 16 receivethe in-line containers 212 and 214 when the tray 48 is mounted on thechassis panel 26. The registered chambers 206/206′ and 208/208′ mutuallyimpose volumetric constraints on the in-line containers 212 and 214, todefine a maximum interior volume for each of the on-line containers 212and 214. In the illustrated embodiment, when facing the chassis panel26, the container 212 is situated on the left side (in registeredchambers 206/206′) and the container 214 is situated on the right side(in registered chambers 208/208′). FIGS. 12A and 12B show one embodimentof the right and left orientation of the containers 212 and 214, withthe containers 212 and 214 also shown in side section.

[0123] In the embodiment shown in FIGS. 12A and 12B, each in-linecontainer 212 and 214 is itself divided along their midline from frontto back by an interior flexible wall 210, to form four compartments. AsFIGS. 12A and 12B show, two of the compartments face the door 28, andare thus designated as front compartments 212F and 214F. The other twocompartments face the chassis panel 26, and will thus be designed asrear compartments 212R and 214R.

[0124] Each in-line container 212 and 214 has a waste side compartmentcommunicating with waste path 66 and a replacement side compartmentcommunicating with the replacement fluid path 68. In the illustratedembodiment, the circuit 56 establishes communication between thebalancing waste branch path 138 and the rear compartments 212R and 214R(which will also be called the waste side compartments). The circuit 56also establishes communication between the balancing replacement branchpath 198 and the front compartments 212R and 214R (which will also becalled the replacement side compartments). In the embodiment illustratedin FIGS. 12A and 12B, fluid enters the compartments from the bottom andexits the compartments from the top. Other flow paths into and from thecompartments can be established, as will be described later.

[0125] The machine 16 includes an inlet valve assembly 216 and an outletvalve assembly 218 on the chassis panel 26, located in association withthe chambers 206 and 208. The circuit 56 in the tray 48 likewiseincludes, for each in-line container 212 and 214, an inlet clamp region220 and an outlet clamp region 222, which govern flow into and out ofthe waste side compartments 212R and 214R. The circuit 56 in the tray 48also includes, for each in-line container 212 and 214, an inlet clampregion 224 and an outlet clamp region 226, which govern flow into andout of the replacement side compartments 212F and 214F.

[0126] When the tray 48 is mounted on the chassis panel 26, the inletand outlet valve assemblies 216 and 218 on the machine 16 engage thecorresponding waste and replacement fluid inlet and outlet clamp regions220, 222, 224, 226 in the circuit 56. The machine 16 toggles theoperation of inlet and outlet valve assemblies 216 and 218 tosynchronize the flow of fluids into and out of the waste side andreplacement side compartments of each in-line container 212 and 214.

[0127] More particularly, for a given in-line container 212 and 214, ina first valve cycle (see FIG. 12A), the waste side inlet valve 220 isopened while the waste side outlet valve 222 is closed. Waste fluid isconveyed by operation of the waste and replacement pump 152 from thewaste path 66 into the waste side compartment of the given in-linecontainer 212 and 214. Simultaneously, for the same in-line compartment212 and 214, the replacement side inlet valve 224 is closed and thereplacement side outlet valve 226 is opened, so that the incoming flowof waste in the waste side compartment displaces the interior wall 210to express a like volume of replacement fluid from the replacement sidecompartment into the venous blood return path 64.

[0128] In a subsequent cycle for the same in-line container 212 and 214,an opposite valve action occurs (see FIG. 12B). The replacement sideinlet valve 224 is opened and the replacement side outlet valve 226 isclosed, and replacement fluid is conveyed into the replacement sidecompartment from the replacement fluid path 68. The incoming replacementfluid displaces the interior wall 210 to express a like volume of wastefluid from the waste side compartment to the waste bag 126 (the wasteside inlet valve 220 now being closed and the waste side outlet valve222 now being opened).

[0129] As FIGS. 12A and 12B show, the valve assemblies work in tandemupon the two in-line containers 212 and 214, with one container 140receiving waste and dispensing replacement fluid, while the othercontainer 142 receives replacement fluid and dispenses waste, and viceversa. In this way, the circuit 56 provides a continuous, volumetricallybalanced flow of waste fluid to the waste bag 126 and replacement fluidto the venous blood return path 64.

[0130] 2. A Circuit Contained in a Double Panel Bag

[0131] The function of the fluid circuit 56 shown in FIGS. 11, 12A, and12B can be realized in various ways. FIGS. 13A to 13C show a fluidcircuit bag 228 made from two overlaying sheets 230A and 230B offlexible medical grade plastic, e.g., poly vinyl chloride (see FIG.13A). When laid flat (see FIG. 13B), the bag 228 defines first andsecond panels 232 and 234 divided along a midline 236. By folding thebag 228 about its midline 236 (see FIG. 13C), the first and secondpanels 232 and 234 are brought into registration in a reverse facingrelationship, with one panel 232 comprising the front of the bag 228 andthe other panel 234 comprising the back of the bag 228.

[0132] The first and second panel 232 and 234 each includes anindividual pattern of seals S formed, e.g., by radio frequency welding.The seals S form fluid flow paths, including the in-line containers 212and 214, peristaltic pump header regions, the sensor regions, and clampregions previously described. The flow paths formed by the pattern ofseals S can comprise all or part of the circuit 56. Pump header tubinglengths 155, 145, and 201 are sealed in placed within the seal pattern Sto form the pump regions 154, 146, and 201, respectively.

[0133] In the illustrated embodiment, as FIG. 14 shows, the seals S onthe first panel 232 are configured to form the flow paths of the circuit56 through which replacement fluid is conveyed from the replacementfluid path 68 to the venous blood return path 64, including the left andright front-facing replacement fluid compartments 212F and 214F. Theseals S on the second panel 234 are configured to form the flow paths ofthe circuit 56 through which waste fluid is conveyed from the waste path66 to the waste bag 126 or drain, including the left and rightrear-facing waste fluid compartments 212R and 214R. Seals S form fourindividual containers, two containers 212F and 214F on the panel 232,and two containers 212R and 214R on the panel 234.

[0134] Once the seal patterns S are formed, the bag 228 is folded overabout its midline 236 (see FIG. 15). The bag 228 places in closeassociation or registry the waste and replacement fluid paths 66 and 68of the circuit 56. The replacement fluid paths 68 of the circuit 56occupy the front panel 232 of the bag 228, and the waste paths 66 of thecircuit 56 occupy the back panel 234 of the bag 228 (or vice versa,depending upon the desired orientation of the bag 228).

[0135] In use, the folded over bag 228 is contained in the base 50 ofthe tray 48, with portions exposed through cutouts 58 in the insert 51for engagement with the machine peristaltic pumps, sensing elements, andclamping elements, in the manner shown in FIG. 10. The remainingportions of the circuit 56 not contained within the bag 228 are formedof tubing and fit into preformed areas in the base 50 of the tray 48 (orformed within another bag) and coupled in fluid communication with theflow paths of the bag 228, to complete the circuit 56 shown in FIG. 10.

[0136] The flow paths formed on the first panel 232 include the balancereplacement fluid paths 198, which lead to and from the replacement sidecompartments 212F and 214F. In the tray 48, the replacement sidecompartments 212F and 214F rest in recesses in the tray base 50. Cutouts58 in the insert 51 expose the pump header regions 200 and 154, toengage the peristaltic waste and replacement pump 152 on the machine 16;the inlet clamp regions 224, to engage the inlet valve assembly 216 onthe machine 16 to control inflow of replacement fluid into thereplacement side compartments 212F and 214F; and the outlet clampregions 226, to engage the outlet valve assembly 218 on the machine 16to control outflow of replacement fluid from the replacement sidecompartments 212F and 214F. The cutouts 58 also expose the sensor region204, to engage the pressure sensor 202 downstream of the waste andreplacement pump 152, and a pressure relief path 240 with exposedpressure relief bypass valve 242, the purpose of which will be describedlater. A small opening 203 formed in the pump header tubing 201 openscommunication with the relief path 240.

[0137] The flow paths formed on the second panel 234 (shown in phantomlines in FIG. 15) include the waste path 138 that lead to and from thewaste side compartments 212R and 214R (for fluid balancing) and thewaste path 136 that bypasses the waste side compartments 212R and 214R(for ultrafiltration). As FIG. 15 shows, when the bag 228 is folded overin the tray 48, the waste compartments 212R and 214R on the waste panel234 and the replacement compartments 212F and 214F on the replacementpanel 232 overlay, so both are exposed through the cutout 58 in theinsert for registry as a unit with the chambers 206 and 208 on thechassis panel 26.

[0138] The flow paths on the waste panel 234 also include the exposedwaste inlet clamp regions 220, to engage the valve assembly 218 tocontrol inflow of waste fluid into the waste compartments 212R and 214R,and the exposed waste outlet clamp regions 222, to engage the valveassembly 216 to control outflow of waste fluid from the wastecompartments 212R and 214R. When the bag 228 is folded over iii the tray48, the inlet clamp regions of the waste compartments 212R and 214Rformed on the waste panel 234 overlay the outlet clamp regions of thereplacement compartments 212F and 214F formed on the replacement panel232, and vice versa.

[0139] The flow paths also includes an exposed pump header region 154,to engage the peristaltic waste and replacement pump 152. When the bag228 is folded over in the tray 48, the exposed pump header regions 200and 154 on the replacement and waste panels 232 and 234 layside-by-side, to accommodate common engagement with the dual headerwaste and replacement pump 152. The flow paths also include the sensorregion 160, to engage the pressure sensor 156 downstream of the wasteand replacement fluid pump 152.

[0140] The flow paths also include the pump header region 146, to engagethe peristaltic ultrafiltration pump 144. When the bag 228 is foldedover in the tray 48, the exposed pump header region 146 for theultrafiltration pump 144 is spaced away from the other pump headerregions of the circuit 56.

[0141] In FIGS. 12A and 12B, the entry paths serving the waste andreplacement compartments are located at the bottom, while the exit pathsserving the waste and replacement compartments are located at the top.This configuration facilitates priming of the compartments. Still, thespaced apart configuration requires eight valve assemblies.

[0142] In FIG. 16, the entry and exit paths serving the waste andreplacement compartments are ail located at the top. Priming is stillachieved, as the paths are top-oriented. Furthermore, due to thefolded-over configuration of the bag itself, the clamping regions 220,222, 226 can be arranged overlay one another. The overlaying arrangementof the clamping regions 220, 222, 224, and 22G serving the waste andreplacement compartments simplifies the number and operation of theinlet and outlet valve assemblies 216 and 218 on the machine 16. Sincethe inlet clamp regions 224 for the replacement compartments 212F and214F overlay the outlet clamp regions 222 for the waste compartments212R and 214R, and vice versa, only four clamping elements 244, 246,248, 250 need be employed to simultaneously open and close theoverlaying eight clamp regions (see FIG. 16). By further stacking (notshown) of the compartments, the clamping elements could be reduced totwo.

[0143] As FIG. 16 shows, the first clamping element 244 is movable intosimultaneous clamping engagement with the inlet clamp region 224 of theleft replacement compartment 212F (on the replacement panel 232) and theoutlet clamp region 222 of the left waste compartment 212R (on the wastepanel 234), closing both. Likewise, the fourth clamping element 250 ismovable into simultaneous clamping engagement with the inlet clampregion 224 of the right replacement compartment 214F (on the replacementpanel 232) and the outlet clamp region 222 of the right wastecompartment 214R (on the waste panel 234), closing both.

[0144] The second clamping element 246 is movable into simultaneousclamping engagement with the outlet clamp region 226 of the leftreplacement compartment 212F (on the replacement panel 232) and theinlet clamp region 220 of the left waste compartment 212R (on the wastepanel 232), closing both. Likewise, the third clamping element 248 ismovable into simultaneous clamping engagement with the outlet clampregion 226 of the right replacement compartment 214F (on the replacementpanel 232) and the inlet clamp region 220 of the right waste compartment214R (on the waste panel 234), closing both.

[0145] The machine 16 toggles operation of the first and third clampingelements 244, 248 in tandem, while toggling operation the second andfourth clamping elements 246, 250 in tandem. When the first and thirdclamping elements 244, 248 are operated to close their respective clampregions, replacement fluid enters the right replacement compartment 214Fto displace waste fluid from the underlying right waste compartment214R, while waste fluid enters the left waste compartment 212R todisplace replacement fluid from the overlaying left replacementcompartment 212F. When the second and fourth clamping elements 246, 250are operated to close their respective clamp regions, replacement fluidenters the left replacement compartment 212F to displace waste fluidfrom the underlying left waste compartment 212R, while waste fluidenters the right waste compartment 214R to displace replacement fluidfrom the overlaying right replacement compartment 214F.

[0146]FIGS. 17 and 18 show a mechanically linked pump and valve system300 that can be arranged on the chassis panel 26 and used in associationwith the layered fluid circuit bag 228 shown in FIG. 15.

[0147] The system 300 includes three electric motors 302, 304, and 306.The first motor 302 is mechanically linked by a drive belt 308 to thedual header waste and replacement pump 152, previously described. Thesecond motor 304 is mechanically linked by a drive belt 310 to the bloodpump 92, also previously described. The third motor 306 is mechanicallylinked by a drive belt 312 to the ultrafiltration pump 144, also aspreviously described.

[0148] A drive belt 314 also mechanically links the first motor to thefirst, second, third, and fourth clamping elements 244, 246, 248, and250, via a cam actuator mechanism 316. The cam actuator mechanism 316includes, for each clamping element 244, 246, 248, and 250 a pinch valve318 mechanically coupled to a cam 320. The cams 320 rotate about a driveshaft 322, which is coupled to the drive belt 314.

[0149] Rotation of the cams 320 advances or withdraws the pinch valves318, according to the surface contour machined on the periphery of thecam 320. When advanced, the pinch valve 318 closes the overlying clampregions of the fluid circuit bag 228 that lay in its path. Whenwithdrawn, the pinch valve 318 opens the overlying clamp regions.

[0150] The cams 320 are arranged along the drive shaft 322 to achieve apredetermined sequence of pinch valve operation. During the sequence,the rotating cams 320 first simultaneously close all the clampingelements 244, 246, 248, and 250 for a predetermined short time period,and then open clamping elements 244 and 248, while closing clampingelements 246 and 250 for a predetermined time period. The rotating cams320 then return all the clamping elements 244, 246, 248, and 250 to asimultaneously closed condition for a short predetermined time period,and then open clamping elements 246 and 250, while closing clampingelements 244 and 248 for a predetermined time period.

[0151] The sequence is repeated and achieves the balanced cycling ofreplacement fluid and waste fluid through the containers 212 and 214, aspreviously described. A chamber cycle occurs in the time interval thatthe valve elements 244, 246, 248, and 250 change from a simultaneouslyclosed condition and return to the simultaneously closed condition.

[0152] The cam actuator mechanism 316 mechanically links the clampingelements 244, 246, 248, and 250 ratiometrically with the first motor302. As the motor 302 increases or decreases the speed of the dualheader waste and replacement pump 152, the operation of the clampingelements 244, 246, 248 and 250 increases or decreases a proportionalamount.

[0153] In a preferred embodiment, the ratio is set so that the flow rateper unit time through the waste pump header region 154 (i.e., throughwaste path 66) approximately equals three-fourths of the volume of thewaste compartment 212R/214R, while maintaining the cycle rate at lessthan 10 cycles per minute. For example, if the chamber volume is 20 cc,the cycle occurs after 15 to 17 cc of waste fluid enters thecompartment.

[0154] In the illustrated embodiment, the waste pump header region 154is made smaller in diameter than the replacement fluid header region200. Thus, during operation of the dual header pump 152, the flow ratethrough the replacement fluid header region 200 (through replacementfluid path 68) will always be larger than the flow rate through thewaste pump header region 154 (through waste path 68). Due to the highflow rate through the replacement fluid path 68, a pressure relief path240 with pressure relief bypass valve 242 is provided, to preventoverfilling. In the illustrated embodiment, the valve 242 is amechanically spring biased pressure regulator, and serves the pressureregulation and bypass function of the machine 16.

[0155] In this arrangement, the in-line compartment that receives wastefluid will fill to approximately three-fourths of its volume during eachcycle, displacing an equal amount of replacement fluid from itscompanion compartment. At the same time, the other in-line compartmentthat receives replacement fluid will fill completely. If the compartmentcompletely fills with replacement fluid before the end of the cycle, thepressure relief bypass valve 242 will open to circulate replacementfluid through the relief path 240 to prevent overfilling. During thenext cycle, waste fluid in the compartment will be completely displacedby the complete fill of replacement fluid in its companion compartment.

[0156] The provision of a higher flow rate in the replacement fluid pathalso facilitates initial priming (as will be described later). Onlyseveral chamber cycles are required to completely prime the in-linecontainers 212 and 214 with replacement fluid before fluid balancingoperations begin.

[0157] The pump and valve system 300 used in association with thelayered fluid circuit bag 228 achieves accurate fluid balancing duringfrequent hemofiltration. Due to the smaller volumes of replacement fluidrequired during each frequent hemofiltration session, slight variationsthat may occur (e.g., plus or minus 5%) between fluid volume removed andfluid volume replaced do not lead to large volume shifts. As a result ofaccurate balancing of small fluid volumes, a person undergoing frequenthemofiltration does not experience significant day-to-day swings in bodyfluid volume, and more precise control of the person's body fluid andweight can be achieved.

[0158] C. Supplying Ancillary Materials

[0159] The system 10 further includes a source 252 or sources thatsupply ancillary materials 20 to the treatment location 12 for use inassociation with the cartridge 18 and machine 16. The ancillarymaterials 20 include the replacement fluid containers 176, as prescribedby the person's physician.

[0160] The ancillary materials 20 may also include an anticoagulantprescribed by a physician. However, anticoagulant may not be requiredfor every person undergoing frequent hemofiltration, depending upontreatment time, treatment frequency, blood hematocrit, and otherphysiologic conditions of the person.

[0161] The ancillary materials 20 can also include the hemofilter 34,although, alternatively, the tray 48 can carry the hemofilter 34, or Thehemofilter 34 can comprise an integrated component of the cartridge 18.

[0162] Through operation of the machine 16, cartridge 18, and ancillarymaterials 20 supplied by the system 10, the person's blood is conveyedthrough the hemofilter 34 for removal of waste fluid containing urea andother toxins. Replacement fluid is exchanged for the removed wastefluid, to maintain the person's electrolyte balance and acid/basebalance. The replacement fluid is also balanced against an additionalwaste fluid removal, to yield a net ultrafiltration loss, as prescribedby the person's physician.

[0163] The composition of an optimal replacement fluid solution usableduring frequent hemofiltration consist of a balanced salt solutioncontaining the major cationic and anionic plasma constituents, includingbicarbonate or another anion from which net bicarbonate can be generatedby metabolism. Specific cationic substances removed by frequenthemofiltration that require replacement typically include sodium,potassium and calcium. Specific anionic substances removed by frequenthemofiltration that require replacement include chloride and eitherbicarbonate or another anion that can be metabolized into bicarbonate,such as acetate, citrate, or, typically, lactate.

[0164] The replacement fluid for frequent hemofiltration should excludephosphorus and other anionic substances. These materials typicallyaccumulate in undesirable amounts in persons experiencing renal failureand are either difficult to remove in large amounts duringhemofiltration or are safely removed without need for specificreplacement.

[0165] The concentration of sodium in a replacement fluid for frequenthemofiltration should fall slightly below that of the typical bloodfiltrate concentration of 135 to 152 meq/liter. The optimal range forsodium in the replacement fluid for frequent hemofiltration is 128-132meq/liter, and typically 130 meq/liter. This concentration allows for anet sodium removal during frequent hemofiltration sessions, which iseasily tolerated due to the smaller replacement fluid volumes necessaryfor frequent hemofiltration. This concentration also results in aminimal net drop in serum osmolality, so as to decrease extracellularvolume to a extent sufficient to maintain euvolemia while amelioratingthirst in the person undergoing frequent hemofiltration.

[0166] The metabolism of calcium is quite complicated and much lessstraightforward than sodium. Thus, the optimal concentration in areplacement fluid for frequent hemofiltration should be much closer tothe normal physiologic range of calcium in plasma, i.e., in a range of2.5 to 3.5 meq/liter, and typically 2.7 meq/liter. This calciumconcentration range is required to prevent tetany, which can result fromexcessive removal of ionized calcium, while removing excessive serumcalcium that may result from the oral calcium supplements and phosphorusbinders frequently used by persons requiring hemofiltration.

[0167] Selecting an optimal concentration of potassium in a replacementfluid for frequent hemofiltration is important. Typically, the potassiumconcentrations selected for replacement fluids used during infrequenthemofiltration (3 times a week or less) or during hemodialysis are quitelow, e.g., in the range of 0 to 3 meq/liter. These low concentrations ofpotassium are required for infrequent hemofiltration therapies, toprevent life threatening accumulations of serum potassium betweentreatment sessions. Interim accumulation of toxic levels of potassiumcan be encountered between infrequent hemofiltration sessions, bothbecause of decreased renal excretion of potassium and the interimdevelopment of acidosis between sessions. This, in turn, can result intotal body potassium depletion in many persons undergoing infrequenttherapy. Potassium depletion results in vasoconstriction and subsequentalterations in regional blood flow. Potassium depletion also interfereswith the efficiency of solute removal, as measured by a decrease in Kt/Vfor urea, which is a dimensionless parameter commonly employed tomeasure the adequacy of dialysis. Potassium depletion is also implicatedin the pathogenesis of hypertension in patients undergoing hemodialysisor infrequent hemofiltration.

[0168] In contrast, the optimal range for potassium in a replacementfluid used for frequent hemofiltration can fall in a higher range thanthat required of less frequent treatment schedules, laying in the rangeof 2.7 to 4.5 meq/liter, and typically 4.0 meq/liter. This higherconcentration of potassium, when infused frequently in smaller fluidreplacement volumes, prevents potassium depletion, while alsomaintaining more stable potassium levels to prevent toxic accumulationof potassium between sessions.

[0169] Additional benefits derived from frequent hemofiltration in thecontrol of serum potassium lay in the more physiologic control ofacidosis, which prevents extra cellular shift of potassium from theintracellular space. In addition to the control of acidosis, theavoidance of total body potassium depletion enhancesaldosterone-mediated gut elimination of potassium, further safeguardingagainst hyperkalemia.

[0170] The optimal range for chloride concentrations in a replacementfluid used for frequent hemofiltration is 105 to 115 meq/liter, andtypically 109 meq/liter. This concentration most closely approximatesthe normal sodium to chloride ratio of 1.38:1 maintained in the plasma.The small deviation from this ratio in the replacement fluid itselfallows for the normalization of the ratio by daily oral intake of theseelectrolytes. Due to the larger replacement fluid volumes needed forinfrequent treatment (three times per week or less), this deviation fromthe normal 1.38:1 ratio are exaggerated, and can lead to ahyperchloremic acidosis. Due to the use of smaller fluid volumes duringeach frequent hemofiltration session, hyperchloremic acidosis can beavoided.

[0171] The optimal range of bicarbonate or an equivalent in areplacement fluid used for frequent hemofiltration is also important.Concentrations must adequately replace filtered bicarbonate whilecontrolling acidosis and avoiding metabolic alkalosis. Because ofprecipitation of calcium carbonate in solutions containing dissolvedcalcium and bicarbonate, bicarbonate itself is generally impractical foruse in a replacement fluid. Other substances such as acetate, citrate,or typically lactate, are substituted. These substances are metabolizedby the body into bicarbonate and do not precipitate when placed intosolution with the cationic substances mentioned previously.

[0172] The range of lactate necessary to replace filtered bicarbonateand control acidosis without alkalemia is 25 to 35 mmoles per liter, andtypically 28 mmoles per liter. Due to the large volumes of replacementfluid used for infrequent therapies, use of lactate containingreplacement fluids can result in lactate accumulation and pathologicalterations in the lactate:pyruvate ratio and resulting in undesirablechanges in cellular redox potentials. However, these effects areminimized by the frequent use of smaller volumes of replacement fluidduring frequent hemofiltration. This also results in more physiologiccontrol of acidosis and, secondarily, serum potassium concentration. Thelatter is accounted for by reduced extra-cellular shift of potassiumcaused by acidosis.

[0173] The above observation also holds true for acetate and citrate, aswell. The typical range of acetate in replacement fluid would be 25 to35 mmoles/liter, and typically 30 mmoles/liter. The typical range ofcitrate would be 16 to 24 mmoles/liter, and typically 20 mmoles/liter.These concentrations render solutions containing acetate impractical forlarge volume replacements on an infrequent basis, because of toxicityincurred by the accumulation of acetate. These include both cardiac andhepatic toxicity. There are additional issues of calcium and magnesiumchelation, which become significant when citrate is used in the largevolumes necessary for infrequent therapy. These toxic effectsattributable to acetate or citrate are minimized by the smallerreplacement volumes required for daily hemofiltration.

[0174] The unique combination of electrolytes and basic substancesdiscussed above represent a novel solution to the problem of choosingreplacement fluid for frequent hemofiltration. The same constituentswould not likely be applicable to less frequent treatment schedules.

[0175] Frequent hemofiltration minimizes the depletion of bloodelectrolytes during each hemofiltration session. Thus, the replacementfluid need not include replacement electrolytes. The source 252 maytherefore supply relatively inexpensive commodity solutions ofphysiologic fluids, free of electrolytes, e.g., normal saline orRinger's lactate (which typically contains 6 mg/ml sodium chloride (130meq/liter); 3.1 mg/ml of sodium lactate (28 meq/liter); 0.3 mg/mlpotassium chloride (4 meq/liter); 0.2 mg/ml calcium chloride (2.7meq/liter, 109 meq/liter at an osmolarity of 272 mos/liter); at a pH of6.0 to 7.5). When buffered with citrate, Ringer's lactate effectivelyachieves the fluid balancing function. The citrate used to buffer theinexpensive, electrolyte-free replacement fluid can also serve theadditional function of anticoagulating the blood as it undergoeshemofiltration in the first place.

[0176] The source 252 supplying the ancillary materials 20 can compriseone or more companies or businesses that manufacture the ancillarymaterials or that otherwise distributes the ancillary materials 20 tothe treatment location 12.

[0177] D. Exemplary Frequent Hemofiltration Modalities

[0178] The system 10 serves to enable frequent hemofiltration with highblood flow rates. The high blood flow rates reduce the processing time,and also significantly increases the transport rate of uremic toxinsacross the hemofiltration membrane. The frequent hemofiltration that thesystem 10 enables removes high concentrations of uremic toxins, withoutrequiring the removal of high fluid volumes, with the attendant loss ofelectrolytes. The system 10 thereby provides multiple benefits for theindividual, i.e., a tolerable procedure time (e.g., about one to twohours), with high clearance of uremic toxins, without high depletion ofliquids and physiologic electrolyte levels in the blood, accurate fluidvolume balancing, and use of inexpensive commodity replacement fluids.

[0179] The machine 16 and cartridge 18 that the system 10 may providecan be used to provide diverse frequent hemofiltration modalities on acontinuous or extended basis, e.g., normal frequent hemofiltration,balanced frequent hemofiltration, only net ultrafiltration, andreplacement fluid bolus.

[0180] During normal frequent hemofiltration, blood is drawn from theperson at a prescribed flow rate (BFR). Waste fluid is removed from thearterial blood flow and volumetrically balanced with replacement fluid,which is returned in the venous blood flow at a prescribed rate (RFR). Aprescribed net ultrafiltration volume of waste fluid is also removed ata prescribed flow rate (UFR) with fluid balancing, to control net weightloss. Operation of the machine 16 in the normal frequent hemofiltrationmode terminates when either (i) the replacement fluid sensor indicatesthe absence of replacement fluid flow by sensing the presence of air(i.e., no more replacement fluid) and the net ultrafiltration goal hasbeen achieved; or (ii) the time prescribed for the session has elapsed.

[0181] During balanced frequent hemofiltration, normal hemofiltrationoccurs without an ultrafiltration function. This mode can be used forpersons that experience no weight gains between treatment sessions. Thismode can also be used at the end of a normal frequent hemofiltrationsession, when the net ultrafiltration goal was achieved beforeexhausting the supply of replacement fluid.

[0182] During only net ultrafiltration, only a net ultrafiltrationvolume of waste is removed from the person. No fluid is replaced. Thismode can be used when it is desired only to remove fluid. This mode canalso be used at the end of a normal frequent hemofiltration session,when the net ultrafiltration goal has not been achieved but the supplyof replacement fluid has been exhausted.

[0183] During replacement fluid bolus, there is no fluid balancing andultrafiltration functions. Blood is circulated in an extracorpeal pathand a bolus of replacement fluid is added. In the illustratedembodiment, the ultrafiltration pump 144 is run in reverse at a speedlower than the waste and replacement pump 152. This recirculates wastefluid through the waste compartments 212R and 214R, to add replacementfluid from the replacement compartments 212F and 214F to the patient.The waste fluid that is recirculated limits waste fluid removal throughthe hemofilter 34, yielding replacement fluid addition withoutadditional waste fluid removal. The net volume of added replacementfluid conveyed to the patient equals the volume of waste fluidrecirculated. This mode can be used to return fluid to a person in abolus volume, e.g., during a hypotensive episode or during rinse back atthe end of a given hemofiltration session.

[0184] 1. Controlling the Blood Flow Rate

[0185] High blood flow rates (e.g., at least 300 ml/min, and preferablyat least 600 ml/min) are conducive to rapid, efficient frequenthemofiltration. The high blood flow rates not only reduce the processingtime, but also significantly increases the transport rate of uremictoxins across the hemofiltration membrane. In this way, the system 10removes high concentrations of uremic toxins, without requiring theremoval of high fluid volumes, with the attendant loss of electrolytes.

[0186] The BFR can be prescribed by an attending physician and input bythe operator at the beginning of a treatment session. Alternatively, themachine 16 can automatically control to achieve an optimal BFR andminimize procedure time, based upon a desired filtration fraction value(FF), FPR, and UFR, as follows: BFR=(RFR+UFR)/FF.

[0187] where:

[0188] FF is the desired percentage of fluid to be removed from theblood stream through the hemofilter 34.

[0189] A desired FF (typically 20% to 35%) can be either preset orprescribed by the attending physician. A desired FF takes into accountthe desired therapeutic objectives of toxin removal, as well as theperformance characteristics of the hemofilter 34. A nominal FF can bedetermined based upon empirical and observed information drawn from apopulation of individuals undergoing hemofiltration. A maximum value of30% is believed to be appropriate for most individuals and hemofilters34, to achieve a desired therapeutic result without clogging of thehemofilter 34.

[0190] In the illustrated embodiment, air leaks into the extracorporealcircuit (due, e.g., to improper patient line connection) is monitored bythe sensor 98. The sensor 98 is an ultrasonic detector, which also canprovide the added capacity to sense flow rate.

[0191] In the illustrated embodiment, the machine 16 senses waste fluidpressure to control the blood flow rate to optimize the removal of fluidacross the hemofilter 34. As arterial blood flows through the hemofilter34 (controlled by the blood pump 92), a certain volume of waste fluidwill cross the membrane into the waste line 11B. The volume of wastefluid entering the waste line 118 depends upon the magnitude of thewaste fluid pressure, which is sensed by the sensor 132. The waste fluidpressure is adjusted by controlling the waste fluid removal rate throughthe fluid balancing compartments (i.e., through control of the waste andreplacement pump 152).

[0192] The machine 16 monitors the waste fluid pressure at sensor 132.By keeping the pressure sensed by the sensor 132 slightly above zero,the machine 16 achieves the maximum removal of fluid from the blood atthen operative arterial flow rate. Waste pressure values significantlyhigher than zero will limit removal of fluid from the blood and keep ahigher percentage of waste fluid in the blood (i.e., result in a lowerfiltration fraction). However, this may be desirable for persons whotend to clot easier.

[0193] By sensing waste fluid pressure by sensor 132, the machine 16also indirectly monitors arterial blood pressure. At a constant bloodpump speed, changes in arterial blood flow caused, e.g., by accessclotting or increased arterial blood pressure, makes less waste fluidavailable in the waste line 118. At a given speed for pump 152, changein arterial blood flow will lower the sensed waste pressure at sensor132 to a negative value, as fluid is now drawn across the membrane. Themachine 16 adjusts for the change in arterial blood flow by correctingthe waste fluid removal rate through the pump 152, to bring the wastepressure back to slightly above zero, or to another set value.

[0194] In this arrangement, a pressure sensor in the arterial blood lineis not required. If the arterial pressure increases at a fixed bloodpump speed, the blood flow must drop, which will result in a sensedrelated drop in the waste fluid pressure by the sensor 132. Adjustingthe pump 152 to achieve a pressure slightly above zero corrects thereduced arterial blood flow. In this arrangement, since the waste fluidpressure is maintained at a slightly positive value, it is not possibleto develop a reverse transmembrane pressure, which conveys waste fluidback to the person's blood. The maximum transmembrane pressure is themaximum venous pressure, since waste fluid pressure is held slightlypositive.

[0195] In an alternative arrangement, arterial blood pressure can bemeasured by a sensor located upstream of the blood pump. The rate of theblood pump is set to maintain sensed arterial blood pressure at apredetermined control point. This controls the blood pump speed to amaximum rate. The control point can be determined by the attendingphysician, e.g., on a day-to-day basis, to take into account thc bloodaccess function of the person undergoing treatment. Use of an arterialpressure control point minimizes the treatment time, or, alternatively,if treatment time is fixed, the removal of waste fluid can maximized.

[0196] In this arrangement, safety alarms can be included should thesensed arterial pressure become more negative than the control point,along with a function to shut down the blood pump should an alarm occur.

[0197] 2. Controlling the Replacement Fluid Flow Rate

[0198] RFR can be prescribed by an attending physician and inputted bythe operator at the beginning of a treatment session.

[0199] Alternatively, the machine 16 can automatically control RFR tominimize procedure time based upon the desired filtration fraction value(FF), BFR, and UFR, as follows: RFR=(BFR*FF)−UFR.

[0200] In the illustrated embodiment, waste is conveyed to the wasteside compartments 212R and 214R, and replacement fluid is conveyed tothe replacement side compartments 212F and 214F, by operation of thedual header waste and replacement fluid pump 152. Alternatively,separate waste and replacement fluid pumps can be provided.

[0201] The speed of the waste and replacement pump 152 is controlled toachieve the desired RFR. The machine 16 cycles the inlet and outletvalve assemblies 216, 218, as described. The machine 16 cycles betweenthe valve states according to the speed of the waste and fluid pump 152to avoid overfilling the compartments 212, 214 receiving fluid. Varioussynchronization techniques can be used.

[0202] In one arrangement, as previously described, the interval of avalve cycle is timed according to the RFR, so that the volume of wasteor replacement fluid supplied to waste compartment during the valvecycle interval is less than volume of the compartment receiving thewaste fluid. Overfilling is thereby avoided without active end of cyclemonitoring. In a preferred embodiment, the waste fluid is pumped at RFR,and the replacement fluid is pumped at a higher rate, but is subject topressure relief through the pressure relief path 240 upon filling thecorresponding replacement side compartment 214.

[0203] In another arrangement, the timing of the transition betweenvalve cycles is determined by active sensing of pressure within thecompartments 212, 214 receiving liquid. As the interior wall 210 reachesthe end of its travel, pressure will increase, signaling an end of cycleto switch valve states.

[0204] In yet another arrangement, the location of the interior wall 210as it reaches the end of its travel is actively sensed by end of cyclesensors on the machine 16. The sensors can comprise, e.g., opticalsensors, capacitance sensors, magnetic Hall effect sensors, or by radiofrequency (e.g., microwave) sensors. The termination of movement of theinterior wall 210 indicates the complete filling of a compartment andthe concomitant emptying of the other compartment, marking the end of acycle. The sensors trigger an end of cycle signal to switch valvestates.

[0205] The machine 16 counts the valve cycles. Since a known volume ofreplacement fluid is expelled from a replacement side compartment duringeach valve cycle, the machine 16 can derive the total replacement volumefrom the number of valve cycles. The replacement fluid volume is alsoknown by the number of replacement fluid bags of known volume that areemptied during a given session.

[0206] Frequent hemofiltration can be conducted without fluidreplacement, i.e., only net ultrafiltration, by setting RFR to zero.

[0207] 3. Controlling the Ultrafiltration Flow Rate

[0208] UFR can be prescribed by an attending physician and inputted bythe operator at the beginning of a treatment session.

[0209] The speed of the ultrafiltration pump is monitored and varied tomaintain UFR.

[0210] Frequent hemofiltration can be conducted without anultrafiltration function, i.e., balanced hemofiltration, by setting UFRto zero.

[0211] 4. Active Filtration Rate Control

[0212] In an alternative embodiment, the machine 16 also activelycontrols the filtration rate along with the blood flow rate, to achievea desired magnitude of uremic toxin removal through the hemofilter 34.

[0213] In this embodiment, the machine 16 includes a flow restrictorwhich is positioned to engage a region of the venous blood return pathin the circuit 56. The restrictor comprises, e.g., a stepper-drivenpressure clamp, which variably pinches a region of the venous bloodreturn path upon command to alter the outlet flow rate of blood. This,in turn, increases or decreases the transmembrane pressure across thefilter membrane.

[0214] For a given blood flow rate, waste transport across the filtermembrane will increase with increasing transmembrane pressure, and viceversa. However, at some point, an increase in transmembrane pressure,aimed at maximizing waste transport across the filter membrane, willdrive cellular blood components against the filter membrane. Contactwith cellular blood components can also clog the filter membrane pores,which decreases waste transport through the membrane.

[0215] Filtration rate control can also rely upon an upstream sensormounted on the machine 16. The sensor is positioned for association witha region of the arterial blood supply path between the blood pump 92 andthe inlet of the hemofilter 34. The sensor senses the hematocrit of theblood prior to its passage through the filter membrane which will becalled the “pre-treatment hematocrit”). In the arrangement, a downstreamsensor is also mounted on the machine 16. The sensor is positioned forassociated with a region of the venous blood return path downstream ofthe outlet of the hemofilter 34. The sensor senses the hematocrit of theblood after its passage through the hemofilter 34 (which will be calledthe “post-treatment hematocrit”).

[0216] The difference between pre-treatment and post-treatmenthematocrit is a function of the degree of waste fluid removal by thehemofilter 34. That is, for a given blood flow rate, the more wastefluid that is removed by the hemofilter 34, the greater the differencewill be between the pre-treatment and post-treatment hematocrits, andvice versa. The machine 16 can therefore derive an actual blood fluidreduction ratio based upon the difference detected by sensors betweenthe pre-treatment and post-treatment hematocrits. The machine 16periodically compares the derived fluid reduction value, based uponhematocrit sensing by the sensors, with the desired FF. The machine 16issues a command to the flow restrictor to bring the difference to zero.

[0217] 5. Set Up Pressure Testing/Priming

[0218] Upon mounting the disposable fluid circuit on the machine 16, thepumps can be operated in forward and reverse modes and the valvesoperated accordingly to establish predetermined pressure conditionswithin the circuit. The sensors monitor build up of pressure within thecircuit, as well as decay in pressure over time. In this way, themachine can verify the function and integrity of pumps, the pressuresensors, the valves, and the flow paths overall.

[0219] The machine 16 can also verify the accuracy of theultrafiltration pump using the fluid balancing containers.

[0220] Priming can be accomplished at the outset of each frequenthemofiltration session to flush air and any residual fluid from thedisposable fluid circuit. Fluid paths from the arterial access to thewaste bag are flushed with replacement fluid. Replacement fluid is alsocirculated through the fluid balancing containers into the waste bag andthe venous return path. The higher flow rate in the replacement fluidpath and timing of the fluid balancing valve elements assure that thereplacement fluid compartments completely fill and the waste fluidcompartments completely empty during each cycle for priming.

[0221] 6. Rinse Back

[0222] As previously described, waste fluid pressure is controlled andmonitored to assure its value is always positive. Likewise, pressurebetween the blood pump and the hemofilter must also be positive, so thatair does not enter this region of the circuit. Forward operation of theblood pump to convey arterial blood into the hemofilter establishes thispositive pressure condition.

[0223] The rinse back of blood at the end of a given frequenthemofiltration procedure can also be accomplished without risk of airentry into the blood flow path. Rinse can be accomplished by stoppingthe blood pump and operating the ultrafiltration pump in the reversebolus mode, as already described. The recirculation of waste fluid bythe ultrafiltration pump through the fluid balancing compartmentsintroduces replacement fluid to flush the venous return line. Whencomplete, the venous clamp is closed.

[0224] With the venous clamp closed, continued operation of theultrafiltration pump in the reverse bolus mode introduces replacementfluid from the fluid balancing compartments into the hemofilter, in aback flow direction through the outlet port. The blood pump is run inreverse to convey the replacement fluid through the hemofilter and intothe arterial blood line. Residual blood is flushed from the blood line.The blood pump is operated in reverse at a rate slower than the reversebolus rate of the ultrafiltration pump (which supplies replacement fluidto the outlet port of the hemofilter), so that air cannot enter theblood path between the blood pump and the hemofilter. At this stage ofthe rinse back, the arterial blood line is also subject to positivepressure between the blood pump and the arterial access, so no air canenter this region, either.

[0225] In this arrangement, no air sensing is required in the arterialblood line and a pressure sensor between the blood pump and thehemofilter is required.

[0226] E. Supplying Telemetry

[0227] The system 10 also preferably includes a telemetry network 22(see FIGS. 1 and 19). The telemetry network 22 provides the means tolink the machine 16 at the treatment location 12 in communication withone or more remote locations 254 via, e.g., cellular networks, digitalnetworks, modem, Internet, or satellites. A given remote location 254can, for example, receive data from the machine 16 at the treatmentlocation 12 or transmit data to a data transmission/receiving device 296at the treatment location 12, or both. A main server 256 can monitoroperation of the machine 16 or therapeutic parameters of the personundergoing frequent hemofiltration. The main server 256 can also providehelpful information to the person undergoing frequent hemofiltration.The telemetry network 22 can download processing or service commands tothe data receiver/transmitter 296 at the treatment location 12.

[0228] Further details about the telemetry aspect of the system 10 willnow be described.

[0229] 1. Remote Information Management

[0230]FIG. 19 shows the telemetry network 22 in association with amachine 16 that carries out frequent hemofiltration. The telemetrynetwork 22 includes the data receiver/transmitter 296 coupled to themachine 16. The data receiver/transmitter 296 can be electricallyisolated from the machine 16, if desired. The telemetry network 22 alsoincludes a main data base server 256 coupled to the datareceiver/transmitter 296 and an array of satellite servers 260 linked tothe main data base server 256.

[0231] The data generated by the machine 16 during operation isprocessed by the data receiver/transmitter 296. The data is stored,organized, and formatted for transmission to the main data base server256. The data base server 256 further processes and dispenses theinformation to the satellite data base servers 260, following bypre-programmed rules, defined by job function or use of the information.Data processing to suit the particular needs of the telemetry network 22can be developed and modified without changing the machine 16.

[0232] The main data base server 256 can be located, e.g., at thecompany that creates or manages the system 10.

[0233] The satellite data base servers 260 can be located, for example,at the residence of a designated remote care giver for the person, or ata full time remote centralized monitoring facility staffed by medicallytrained personnel, or at a remote service provider for the machine 16,or at a company that supplies the machine 16, or the processingcartridge 18, or the ancillary processing material to the treatmentlocation 12.

[0234] Linked to the telemetry network 22, the machine 16 acts as asatellite. The machine 16 performs specified therapy tasks whilemonitoring basic safety functions and providing the person at thetreatment location 12 notice of safety alarm conditions for resolution.Otherwise, the machine 16 transmits procedure data to the telemetrynetwork 22. The telemetry network 22 relieves the machine 16 from majordata processing tasks and related complexity. It is the main data baseserver 256, remote from the machine 16, that controls the processing anddistribution of the data among the telemetry network 22, including theflow of information and data to the person undergoing therapy. Theperson at the treatment location 12 can access data from the machine 16through the local date receiver/transmitter 296, which can comprise alaptop computer, handheld PC device, web tablet, or cell phone.

[0235] The machine 16 can transmit data to the receiver/transmitter 296in various ways, e.g., electrically, by phone lines, optical cableconnection, infrared light, or radio frequency, using cordlessphone/modem, cellular phone/modem, or cellular satellite phone/modem.The telemetry network 22 may comprise a local, stand-alone network, orbe part of the Internet.

[0236] For example, when the machine 16 notifies the person at thetreatment location 12 of a safety alarm condition, the safety alarm andits underlying data will also be sent to the main server 256 on thetelemetry network 22 via the receiver/transmitter 296. While the personundergoing therapy or the care giver works to resolve the alarmcondition, the main server 256 determines, based upon the prevailingdata rule, whether the alarm condition is to be forwarded to otherservers 260 in the network 22.

[0237] When an alarm condition is received by the main server 256, themain server 256 can locate and download to the receiving device 296 theportion of the operator's manual for the machine that pertains to thealarm condition. Based upon this information, and exercising judgment,the operator/user can intervene with operation of the machine 16. Inthis way, the main server 256 can provide an automatic,context-sensitive help function to the treatment location 12. Thetelemetry network 22 obviates the need to provide on-boardcontext-sensitive help programs for each machine 16. The telemetrynetwork 22 centralizes this help function at a single location, i.e., amain server 256 coupled to all machines 16.

[0238] The telemetry network 22 can relay to an inventory server 262supply and usage information of components used for frequenthemofiltration at each treatment location 12. The server 262 canmaintain treatment site-specific inventories of such items, such ascartridges 18, replacement fluid, and hemofilters 34. The company orcompanies of the system 10 that supply the machine 16, or the processingcartridge 18, or the ancillary processing material to the treatmentlocation 12 can all be readily linked through the telemetry network 22to the inventory server 262. The inventory server 262 therebycentralizes inventory control and planning for the entire system 10,based upon information received in real time from each machine 16 ateach treatment location 12.

[0239] The telemetry network 22 can relay to a service server 264hardware status information for each machine 16 at every treatmentlocation 12. The service server 264 can process the informationaccording to preprogrammed rules, to generate diagostic reports, servicerequests or maintenance schedules. The company or companies of thesystem 10 that supply or service the machine 16 can all be readilylinked through the telemetry network 22 to the service server 264. Theservice server 264 thereby centralizes service, diagnostic, andmaintenance functions for the entire system 10. Service-relatedinformation can also be sent to the treatment location 12 via thereceiving device 296.

[0240] The telemetry network 22 can also relay to a treatment monitoringserver 266, treatment-specific information pertaining to thehemofiltration therapy provided by each machine 16 for the person ateach treatment location 12. Remote monitoring facilities 268, staffed bymedically trained personnel, can be readily linked through the telemetrynetwork 22 to the treatment monitoring server 266. The monitoring server266 thereby centralizes treatment monitoring functions for all treatmentlocations 12 served by the system 10. Treatment-monitoring informationcan also be sent to the treatment location 12 via the receiving device296.

[0241] The telemetry network 22 can also provide through the device 296an access portal for the person undergoing frequent hemofiltration tothe myriad services and information contained on the Internet, e.g.,over the web radio and TV, video, telephone, games, financialmanagement, tax services, grocery ordering, prescriptions purchases,etc. The main server 256 can compile diagnostic, therapeutic, and/ormedical information to create a profile for each person served by thesystem 10 to develop customized content for that person. The main server256 thus provide customized ancillary services such as on line training,billing, coaching, mentoring, and provide a virtual community wherebypersons using the system 10 can contact and communicate via thetelemetry network 22.

[0242] The telemetry network 22 thus provides the unique ability toremotely monitor equipment status, via the internet, then provideinformation to the user, also via the internet, at the location of theequipment. This information can includes, e.g., what page on theoperator's manual would be the most helpful for their currentoperational situation, actual data about the equipment's performance(e.g., could it use service, or is it set up based on the caretaker'srecommendations, data about the current session i.e., buttons pressed,alarms, internal machine parameters, commands, measurements.

[0243] The remote site can monitor the equipment for the same reasonsthat the user might. It can also retrieve information about the machinewhen it is turned off because the telemetry device is self-powered. Itretains all information about the machine over a period of time (muchlike a flight recorder for an airplane).

[0244] 2. On Site Programming

[0245] (i) Using the Telemetry Network

[0246] The main server 256 on the telemetry network 22 can also storeand download to each machine 16 (via the device 296) the system controllogic and programs necessary to perform a desired frequenthemofiltration procedure. Programming to alter a treatment protocol tosuit the particular needs of a single person at a treatments site can bedeveloped and modified without a service call to change the machine 16at any treatment location 12, as is the current practice. System widemodifications and revisions to control logic and programs that conditiona machine 16 to perform frequent hemofiltration can be developed andimplemented without the need to retrofit each machine 16 at alltreatment locations 12 by a service call. This approach separates theimparting of control functions that are tailored to particularprocedures, which can be downloaded to the machine 16 at time of use,from imparting safety functions that are generic to all procedures,which can be integrated in the machine 16.

[0247] (ii) Using the Cartridge

[0248] Alternatively, the control logic and programs necessary toperform a desired frequent hemofiltration procedure can be carried in amachine readable format on the cartridge 18. Scanners on the machine 16automatically transfer the control logic and programs to the machine 16in the act of loading the cartridge 18 on the machine 16. Bar code canbe used for this purpose. Touch contact or radio frequency siliconmemory devices can also be used. The machine 16 can also include localmemory, e.g., flash memory, to download and retain the code.

[0249] For example, as FIG. 2 shows, the machine 16 can include one ormore code readers 270 on the chassis panel 26. The tray 48 carries,e.g., on a label or labels, a machine readable (e.g., digital) code 272(see FIG. 10) that contains the control logic and programs necessary toperform a desired frequent hemofiltration procedure using the cartridge18. Loading the tray 48 on the machine 16 orients the code 272 to bescanned by the reader(s) 270. Scanning the code 272 downloads thecontrol logic and programs to memory. The machine 16 is therebyprogrammed on site.

[0250] The code 272 can also include the control logic and programsnecessary to monitor use of the the cartridge 18. For example, the code272 can provide unique identification for each cartridge 18. The machine16 registers the unique identification at the time it scans the code272. The machine 16 transmits this cartridge 18 identificationinformation to the main server 256 of the telemetry network 22. Thetelemetry network 22 is able to uniquely track cartridge 18 use by theidentification code throughout the system 10.

[0251] Furthermore, the main server 256 can include preprogrammed rulesthat prohibit multiple use of a cartridge 18, or that limit extendeduses to a prescribed period of time. An attempted extended use of thesame cartridge 18 on any machine 16, or an attempted use beyond theprescribed time period, will be detected by the machine 16 or the mainserver 256. In this arrangement, the machine 16 is disabled until anunused cartridge 18 is loaded on the machine 16.

[0252] Service cartridges can also be provided for the machine 16. Aservice cartridge carries a code that, when scanned by the reader orreaders on the chassis panel 26 and downloaded to memory, programs themachine 16 to conduct a prescribed service and diagnostic protocol usingthe service cartridge 18.

[0253] (iii) Using an Overlay

[0254] Alternatively, or in combination with any of the foregoingon-site machine 16 programming techniques, the chassis panel 26 can beconfigured to receive overlays 274, 276, 278, 280 (see FIG. 20), whichare specific to particular hemofiltration modalities or therapies thatthe machine 16 can carry out. For example, in the context of theillustrated embodiment, one overlay 274 would be specific to the normalfrequent hemofiltration mode, a second overlay 276 would be specific tothe balanced frequent hemofiltration mode, a third overlay 278 would bespecific to the only net ultrafiltration mode, and a fourth overlay 280would be specific to the replacement fluid bolus mode. Other overlayscould be provided, e.g., for a pediatric hemofiltration procedure, or aneo-natal hemofiltration procedure.

[0255] When a treatment location 12 wants to conduct a particularhemofiltration modality, the treatment location 12 mounts the associatedoverlay on the chassis panel 26. Each overlay contains a code 282 or achip imbedded in the overlay that is scanned or discerned by one or morereaders 284 on the chassis panel 26 after the overlay is mounted on thechassis panel 26. The code 282 is downloaded to flash memory on themachine 16 and programs the machine 16 to conduct hemofiltration in thatparticular mode.

[0256] A person at the treatment location 12 mounts the appropriateoverlay 274, 276, 278, 280 and then mounts a cartridge 18 on the chassispanel 26. The machine 16 is then conditioned by the overlay and madecapable by the cartridge 18 to conduct that particular mode ofhemofiltration using the cartridge 18. In this way, a universalcartridge 18, capable of performing several hemofiltration modes, can beprovided. It is the overlay that conditions the machine 16 to performdifferent treatment modalities. Alternatively, the operator can link theoverlay, machine, and cartridge together by therapy type.

[0257] Furthermore, treatment-site specific alterations of generichemofiltration modes can be developed and implemented. In thisarrangement, treatment-site specific overlays 286 are provided for themachine 16. The treatment site-specific overlay 286 carries a code 282or a chip imbedded in the overlay that, when downloaded by the machine16, implements a particular variation of the hemofiltration mode for theperson at that treatment location 12, as developed, e.g., by anattending physician. A person at the treatment location 12 mounts thetreatment-site specific overlay 286 and then mounts a universalcartridge 18 on the chassis panel 26. The machine 16 is conditioned bythe treatment site-specific overlay 286 and made capable by theuniversal cartridge 18 to conduct that particular specific mode ofhemofiltration using the cartridge 18.

[0258] An additional overlay 288 can be provided that contains code 282or a chip imbedded in the overlay that, when scanned by the reader(s)284 on the chassis panel 26 and downloaded to flash memory, programs themachine 16 to conduct a prescribed service and diagnostic protocol usingthe cartridge 18, which is also mounted on the chassis panel 26.

[0259] F. Extended Use of the Cartridge

[0260] The consolidation of all blood and fluid flow paths in a single,easily installed cartridge 18 avoids the potential of contamination, byminimizing the number of connections and disconnections needed during ahemofiltration session. By enabling a dwell or wait mode on the machine16, the cartridge 18 can remain mounted to the machine 16 after onehemofiltration session for an extended dwell or break period and allowreconnection and continued use by the same person in a subsequentsession or in a continuation of a session following x-rays or testing.

[0261] The cartridge 18 can therefore provide multiple intermittenttreatment sessions during a prescribed time period, without exchange ofthe cartridge 18 after each treatment session. The time of use confinesare typically prescribed by the attending physician or technical stafffor the treatment center to avoid biocontamination and can range, e.g.,from 48 hours to 120 hours, and more typically 72 to 80 hours. Thecartridge 18 can carry a bacteriostatic agent that can be returned tothe patient (e.g., an anticoagulant, saline, ringers lactate, oralcohol) and/or be refrigerated during storage.

[0262] To reduce the change of biocontamination, the cartridge 18 caninclude one or more in-line sterilizing filters 178 (e.g., 0.2 m) inassociation with connectors that, in use, are attached to outside fluidsources, e.g., the replacement fluid source. As FIG. 11 shows, thefilter 178 can be pre-attached to the cartridge 18 and be coupled to amultiple connection set 290, which itself is coupled to the prescribednumber of replacement fluid bags 176. Alternative (as FIG. 21 shows), aseparate customized filtration set 292 can be provided, which attachesto the connector 174 carried by the cartridge 18. The filtration set 292includes a sterilizing filter 178 to which an array of multipleconnector leads 294 is integrated.

[0263] In the dwell mode of the machine 16, fluid can be recirculatedeither continuously or intermittently through the circuit 56. The fluidcan be circulate past a region of ultraviolet light carried on themachine 16 to provide a bacteriostatic effect. Alternatively, or incombination with exposure to ultraviolet light, the fluid can carry abacteriostatic agent, such as an anticoagulant, saline, ringers lactate,or alcohol, which can be returned to the person at the beginning of thenext treatment session. The machine 16 and cartridge 18 can also besubjected to refrigeration during the dwell period.

[0264] In an alternative embodiment, an active disinfecting agent can becirculated through the circuit 56 during the dwell period. Thedisinfecting material can include a solution containing AmuchinaJmaterial. This material can be de-activated by exposure to ultravioletlight prior to the next treatment session. Exposure to ultraviolet lightcauses a chemical reaction, during which Amuchinaj material breaks downand transforms into a normal saline solution, which can be returned tothe person at the start of the next hemofiltration session.

[0265] G. The Operator Interface

[0266]FIG. 22 shows a representative display 324 for an operatorinterface 44 for the machine. The display 324 comprises a graphical userinterface (GUI), which, in the illustrated embodiment, is displayed bythe interface 44 on the exterior of the door 28, as FIG. 2 shows. TheGUI can be realized, e.g., as a membrane switch panel, using anicon-based touch button membrane. The GUI can also be realized as a “C”language program implemented using the MS WINDOWS™ application and thestandard WINDOWS 32 API controls, e.g., as provided by the WINDOWS™Development Kit, along with conventional graphics software disclosed inpublic literature.

[0267] The GUI 324 presents to the operator a simplified informationinput and output platform, with graphical icons, push buttons, anddisplay bars. The icons, push buttons, and display bars are preferablyback-lighted in a purposeful sequence to intuitively lead the operatorthrough set up, execution, and completion of a frequent hemofiltrationsession.

[0268] The GUI 324 includes an array of icon-based touch button controls326, 328, 330, and 332. The controls include an icon-based treatmentstart/select touch button 326, an icon-based treatment stop touch button328, and an icon-based audio alarm mute touch button 330. The controlsalso include an icon-based add fluid touch button 332 (for prime, rinseback, and bolus modes, earlier described).

[0269] An array of three numeric entry and display fields appear betweenthe icon-based touch buttons. The fields comprise information displaybars 334, 336, and 338, each with associated touch keys 340 toincrementally change the displayed information. In the illustratedembodiment, the top data display bar 334 numerically displays theReplacement Fluid Flow Rate (in ml/min), which is the flow rate forremoving waste fluid and replacing it with an equal volume ofreplacement fluid. The middle data display bar 336 numerically displaysthe ultrafiltration flow rate (in kg/hr), which is the flow rate forremoving waste fluid to control net weight loss. The bottom data displaybar 338 numerically displays the Blood Pump Flow Rate (in ml/min).

[0270] The associated touch keys 340 point up (to increase the displayedvalue) or down (to decrease the displayed value), to intuitivelyindicate their function. The display bars 334, 336, and 338 and touchkeys 340 can be shaded in different colors, e.g., dark blue for thereplacement flow rate, light blue for ultrafiltrational flow rate, andred for the blood flow rate.

[0271] An array of status indicator bars appears across the top of thescreen. The left bar 342, when lighted, displays a “safe” color (e.g.,green) to indicate a safe operation condition. The middle bar 344, whenlighted, displays a “cautionary” color (e.g., yellow) to indicate acaution or warning condition and may, if desired, display a numeric orletter identifying the condition.

[0272] The right bar 346, when lighted, displays an “alarm” color (e.g.,red) to indicate a safety alarm condition and may, if desired, display anumeric or letter identifying the condition.

[0273] Also present on the display is a processing status touch button348. The button 348, when touched, changes for a period of time (e.g., 5seconds) the values displayed in the information display bars 334, 336,and 338, to show the corresponding current real time values of thereplacement fluid volume exchanged (in the top display bar 334), theultrafiltrate volume (in the middle display bar 336), and the bloodvolume processed (in the bottom display bar 338). The status button 348,when touched, also shows the elapsed procedure time in the left statusindicator bar 342.

[0274] The display also includes a cartridge status icon 350. The icon350, when lighted, indicates that the cartridge 18 can be installed orremoved from the machine 16.

[0275] The GUI 324, though straightforward and simplified, enables theoperator to set the processing parameters for a given treatment sessionin different ways.

[0276] For example, in one input mode, the GUI 324 prompts the operatorby back-lighting the replacement fluid display bar 334, theultrafiltration display bar 336, and the blood flow rate display bar338. The operator follows the lights and enters the desired processingvalues using the associated touch up/down bottons 340. The GUIback-lights the start/select touch button 326, prompting the operator tobegin the treatment. In this mode, the machine 16 controls the pumps toachieve the desired replacement fluid, ultrafiltration, and blood flowrates set by the operator. The machine terminates the procedure when allthe replacement fluid is used and the net ultrafiltration goal isachieved.

[0277] In another input mode, the operator can specify individualprocessing objectives, and the machine 16 will automatically set andmaintain appropriate pump values to achieve these objectives. This modecan be activated, e.g., by pressing the start/select touch button 326while powering on the machine 16. The GUI 324 changes the function ofthe display bars 334 and 336, so that the operator can select and changeprocessing parameters. In the illustrated embodiment, the processingparameters are assigned identification numbers, which can be scrolledthrough and selected for display in the top bar 334 using the touchup/down keys 340. The current value for the selected parameter isdisplayed in the middle display bar 336, which the operator can changeusing the touch up/down keys 340.

[0278] In this way, the operator can, e.g., specify a desired filtrationfactor value (FF) along with a desired ultrafiltration flow rate (UFR)and replacement fluid flow rate (RFR). The machine will automaticallycontrol the blood pump rate (BFR), based upon the relationshipBFR=(RFR+UFR)/FF, as previously described.

[0279] Alternatively, the operator can specify a desired filtrationfactor value (FF) along with a desired ultrafiltration flow rate (UFR)and blood flow rate (BFR). The machine will automatically control thereplacement fluid pump rate (RFR), based upon the relationshipRFR=(BFR*FF)−UFR, as already described.

[0280] Alternatively, the operator can specify only an ultrafiltrationvolume. In this arrangement, the machine 16 senses waste fluid pressureto automatically control the blood flow rate to optimize the removal offluid across the hemofilter 34, as previously described. Alternatively,the machine can automatically control the blood flow rate to optimizeremoval of fluid based a set control arterial blood pressure, as alsoalready described.

[0281] As FIG. 22 shows, the interface also preferably includes aninfrared port 360 to support the telemetry function, as previouslydescribed.

[0282] As FIG. 23 shows, the interface 44 can include a generic displaypanel 352 that receives a family of templates 354. Each template 354contains code 356 or chip that, when scanned or discerned by a reader358 on the interface panel 352, programs the look and feel of theinterface 44. In this way, a generic display panel 352 can serve tosupport a host of different interfaces, each optimized for a particulartreatment modality.

[0283] Various features of the invention are set forth in the followingclaims.

We claim:
 1. A renal replacement therapy system, comprising: a fluidcircuit and blood treatment device in which an ingoing fluid issupplied, and an outgoing fluid is generated, in relation to a treatmentprocess of said blood treatment device; the blood treatment engagingsaid fluid circuit to effect first and second cycles of operation wherethe fluid circuit has at least one chamber that displaces the outgoingfluid with the ingoing fluid during the first cycle and displace theingoing fluid with the outgoing going fluid during the second cycle, theoutgoing fluid being disposed of during said first and second cyclessuch that said ingoing and outgoing fluids remain in substantialbalance; the blood treatment device effecting a third cycle in which itrecirculates the outgoing fluid rather than disposing of it such thatsaid ingoing fluid is displaced and thereby supplied to said bloodtreatment process without a corresponding quantity of outgoing fluidbeing generated thereby.
 2. A system as in claim 1, wherein said thirdcycle includes fourth cycle in which said recirculated outgoing fluid isdisplaced with the ingoing fluid during the first cycle and a fifthcycle in which the ingoing fluid is displaced with the recirculatedoutgoing fluid.
 3. A system as in claim 1, wherein said blood treatmentdevice effects a fourth cycle in at least some of said outgoing fluidbypasses said at least one chamber to reduce a quantity of said ingoingfluid displaced by it such that said ingoing and outgoing fluids aresubstantially unbalanced during said fourth cycle.
 4. A renalreplacement therapy system, comprising: a fluid circuit and bloodtreatment device in which an ingoing fluid is supplied, and an outgoingfluid is generated, in relation to a treatment process of said bloodtreatment device; the blood treatment engaging said fluid circuit toeffect first and second cycles of operation where the fluid circuit hasat least one chamber that displaces the outgoing fluid with the ingoingfluid during the first cycle and displace the ingoing fluid with theoutgoing going fluid during the second cycle, the outgoing fluid beingdisposed of during said first and second cycles such that said ingoingand outgoing fluids remain in substantial balance; the blood treatmentdevice effecting a third cycle in which at least a portion of saidoutgoing fluid is circulated back is recirculated to shift saidsubstantial balance is tilted in favor of said ingoing fluid, a resultof said shift being to cause additional fluid to be infused into apatient being subjected to said treatment process.
 5. A system as inclaim 4, wherein blood treatment device effects a fourth cycle in whichat least some of said outgoing fluid bypasses said at least one chambercausing said ingoing and outgoing fluids to be out of balance in favorof said outgoing fluid during said fourth cycle.
 6. A fluid replacementsystem, comprising: blood treatment apparatus that generates outgoingfluid and consumes ingoing fluid; a chamber including an interior walldividing the chamber into a first compartment to retain a volume ofoutgoing fluid and a second compartment to retain a volume of ingoingfluid, the interior wall responding to differential fluid pressure todisplace outgoing fluid from the first compartment as ingoing fluid isconveyed into the second compartment and vice versa, an outgoing line toconduct outgoing fluid, a first pump assembly communicating with theoutgoing line and the first compartment, a second pump assemblycommunicating with a source of ingoing fluid and the second compartment,a third pump assembly communicating with the outgoing line and the firstcompartment in at a location upstream of the first pump assembly, and acontroller coupled to the first, second, and third pump assemblies,being operable in a first cycle, during which the first and second pumpassemblies are operated to convey a volume of outgoing fluid into thefirst compartment to displace a volume of ingoing fluid from the secondcompartment, the controller also being operable in a second cycle,during which the first and second pump assemblies are operated to conveya volume of ingoing fluid into the second compartment to displace avolume of outgoing fluid from the first compartment, the controllerbeing selectively operable during the first and second cycles to operatethe third pump assembly in a bolus mode, during which a volume ofoutgoing fluid is recirculated from the first compartment into theoutgoing line to displace ingoing fluid from the second compartmentwhile limiting removal of additional outgoing fluid by the bloodtreatment apparatus.
 7. A system according to claim 6, wherein thecontroller is selectively operable to operate the third pump assembly inan ultrafiltration mode, during which outgoing fluid is conveyed fromthe outgoing line in a path that bypasses the first pump assembly.
 8. Asystem according to claim 7, wherein the controller is operable in theultrafiltration mode during the first and second cycles.
 9. A systemaccording to claim 6, wherein the controller operates during the firstand second cycles to achieve a predetermined volumetric balance betweenwaste fluid conveyed into the first compartment and replacement fluidconveyed from the second compartment, and vice versa.
 10. A systemaccording to claim 6, wherein the controller is operable to maintainprescribed pump rates for the first, second, and third pump assemblies,and wherein, during the bolus mode, the pump rate prescribed for thethird pump assembly is less than the pump rate prescribed for either thefirst pump assembly or the second pump assembly.
 11. A fluid replacementsystem for use with a blood treatment process, comprising: a balancingmechanism with a first pumping portion to eject an outgoing fluidreceived from a blood processing component; a controller and a flowcircuit permitting outgoing fluid ejected thereby to be selectivelyconveyed either to a outgoing receiver or recirculated back to saidfirst pumping portion; said balancing mechanism also having a secondpumping portion receiving and ejecting ingoing fluid, a rate of saidejecting ingoing fluid being appropriate for infusion into a patientduring a blood treatment; said first and second pumping portions beingmechanically interconnected such that outgoing fluid received by saidfirst pumping portion displaces ingoing fluid in said second pumpingportion, thereby determining a rate at which said ingoing fluid isejected from said second pumping section; said controller beingconfigured to recirculate said outgoing fluid at at least one pointduring a treatment, in response to a command to provide extra ingoingfluid to said patient.
 12. A system as in claim 10, wherein said bloodtreatment process includes hemofiltration.
 13. A fluid replacementsystem for use with a blood treatment process, comprising: a balancingmechanism with a first pumping portion connectable to a blood treatmentportion and operable to receive and eject outgoing fluid therefrom; acontroller and a flow circuit permitting outgoing fluid ejected therebyto be selectively conveyed either to a outgoing receiver or recirculatedback to said first pumping portion; said balancing mechanism also havinga second pumping portion receiving and ejecting ingoing fluid; saidfirst and second pumping portions being mechanically interconnected suchthat outgoing fluid received by said first pumping portion displacesingoing fluid in said second pumping portion, thereby determining a rateat which said ingoing fluid is ejected from said second pumping section;said controller being configured to recirculate said outgoing fluid atat least one point during a treatment, in response to a command toprovide extra ingoing fluid to said patient; wherein said first andsecond pumping portions each include at least one flexible chamber, saidfirst pumping portion flexible chamber pressing against said secondpumping portion flexible chamber when said first pumping portionflexible chamber fills with outgoing.
 14. A fluid replacement system foruse with a blood treatment process, comprising: a blood treatment devicegenerating outgoing fluid and consuming ingoing fluid; a balancingmechanism configured such that said outgoing fluid displaces saidingoing fluid at a volume rate equal to a rate at which said outgoingfluid is received by said balancing mechanism; a flow circuit beingconfigured to convey outgoing fluid ejected from said balancingmechanism to be selectively conveyed to at least one of said outgoinginlet and a outgoing receiver responsively to a controller; saidcontroller being configured to convey at said some of said outgoingfluid to said outgoing inlet, in response to a command to provide avolume of ingoing fluid, whereby said at least some of said outgoingfluid may displace said ingoing fluid in said balancing mechanismwithout a corresponding amount of outgoing fluid being received by saidbalancing mechanism.
 15. A system as in claim 14, wherein said bloodtreatment process includes hemofiltration.
 16. A system as in claim 14,wherein said blood treatment device includes a hemofilter.
 17. A systemas in claim 14, wherein said positive displacement balancing mechanismincludes at least two flexible chambers, a first of which receivesoutgoing, a second of which receives ingoing fluid, said positivedisplacement balancing mechanism being configured such that said firstflexible chamber presses against said second flexible chamber todisplace said ingoing fluid in proportion to an amount of outgoing fluidreceived thereat.